EP0627427A1 - 3-Quinolyl substituted dihydropyridines, process for their preparation and their use in drugs - Google Patents

Abstract

The invention relates to new 3-quinolyl-substituted dihydropyridines of the general formula (I) <IMAGE> in which R1 to R5 have the meaning given in the description, process for their preparation and their use in drugs, in particular in compositions for the treatment of cardiovascular disorders.

Description

The invention relates to new 3-quinolyl-substituted dihydropyridines, processes for their preparation and their use in medicaments, in particular in agents for the treatment of cardiovascular diseases.

It is already known that 1,4-dihydropyridines have vasodilatory properties and can be used as coronary agents and antihypertensives. It is also known that 1,4-dihydropyridines inhibit the contractile force of smooth and cardial muscles and can be used to treat coronary and vascular diseases.

Furthermore, 4-quinolyl-dihydropyridines with a positive inotropic effect are already known from US Pat.

in welcher

• R¹ und R⁴ gleich oder verschieden sind und für Wasserstoff, Amino, Cyano, Formyl, Trifluormethyl oder für geradkettiges oder verzweigtes Alkyl mit bis zu 8 Kohlenstoffatomen stehen, das gegebenenfalls durch Hydroxy oder durch eine Gruppe der Formel -NR⁶R⁷, - O-CO-R⁸, -O-(CH₂)_a-OR^8' oder -0-(CH₂)_b-NR⁹R'⁰ substituiert ist, worin
• R⁶, R⁷, R⁹ und R¹⁰ gleich oder verschieden sind und Wasserstoff, Phenyl oder geradkettiges oder verzweigtes Alkyl mit bis zu 6 Kohlenstoffatomen bedeuten,
• R⁸ und R⁸' gleich oder verschieden sind und geradkettiges oder verzweigtes Alkyl mit bis zu 6 Kohlenstoffatomen bedeuten, und
• a und b gleich oder verschieden sind und eine Zahl 2, 3, 4 oder 5 bedeuten,
• R² für eine Gruppe der Formel - CO-NR¹¹R¹² oder -CO-A-R¹³ steht, worin
• R¹¹ und R¹² gleich oder verschieden sind und Wasserstoff, einen geradkettigen, verzweigten oder cyclischen, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 8 Kohlenstoffatomen bedeuten, der gegebenenfalls durch Halogen, Hydroxy, Cyano oder durch Aryl, Aryloxy, Arylthio mit jeweils 6 bis 10 Kohlenstoffatomen oder durch einen 5- bis 7-gliedrigen, gesättigen oder ungesättigten Heterocyclus mit bis zu 3 Heteroatomen aus der Reihe S, N oder O substituiert ist, wobei die Cyclen ihrerseits durch Halogen, Cyano oder durch geradkettiges oder verzweigtes Alkyl, Alkoxy, Alkylthio, Alkoxycarbonyl, Halogenalkyl, Halogenalkoxy oder Halogenalkylthio mit jeweils bis zu 4 Kohlenstoffatomen substituiert sein können, oder Aryl mit 6 bis 10 Kohlenstoffatomen oder einen 5-bis 7-gliedrigen, gesättigten oder ungesättigten Heterocyclus mit bis zu 3 Heteroatomen aus der Reihe S, N oder O bedeuten, die gegebenenfalls bis zu 2-fach gleich oder verschieden durch Halogen, Cyano oder durch geradkettiges oder verzweigtes Alkyl, Alkoxy, Alkylthio, Alkoxycarbonyl, Halogenalkyl, Halogenalkoxy oder Halogenalkylthio mit jeweils bis zu 4 Kohlenstoffatomen substituiert sind, oder
• R¹¹ und R¹² gemeinsam unter Einbezug des Stickstoffatoms einen 3-bis 8-gliedrigen, gesättigen oder ungesättigten Heterocyclus bilden, der gegebenenfalls durch ein Sauerstoffatom oder durch einen Rest der Formel S(O)_d, -CO- oder -NR¹⁵ unterbrochen sein kann, worin
• d eine Zahl 0, 1 oder 2 bedeutet,
• R¹⁵ Wasserstoff oder Aryl mit 6 bis 10 Kohlenstoffatomen bedeutet, das gegebenenfalls bis zu 2-fach gleich oder verschieden durch Halogen, Cyano oder durch geradkettiges oder verzweigtes Alkyl, Alkoxy, Alkylthio Alkoxycarbonyl mit jeweils bis zu 8 Kohlenstoffatomen, Halogenalkyl, Halogenalkoxy oder Halogenalkylthio mit jeweils bis zu 4 Kohlenstoffatomen substituiert ist, oder
  einen cyclischen, gesättigten oder ungesättigten, geradkettigen oder verzweigten Kohlenwasserstoffrest mit bis zu 8 Kohlenstoffatomen bedeutet, der gegebenenfalls durch Hydroxy, Halogen oder durch Aryl mit 6 bis 10 Kohlenstoffatomen oder einen 5-bis 7-gliedrigen, gesättigen oder ungesättigten Heterocyclus mit bis zu 3 Heteroatomen aus der Reihe S, N oder O substituiert ist, wobei die Cyclen ihrerseits bis zu 2-fach gleich oder verschieden durch Halogen, Cyano oder durch geradkettiges oder verzweigtes Alkyl, Alkoxy, Alkylthio, Alkoxycarbonyl, Halogenalkyl, Halogenalkoxy oder Halogenalkylthio mit jeweils bis zu 4 Kohlenstoffatomen substituiert sein können,
  und der Heterocyclus gegebenenfalls durch geradkettiges oder verzweigtes Alkoxy oder Alkylthio mit jeweils bis zu 4 Kohlenstoffatomen, Halogen, Aryl mit 6 bis 10 Kohlenstoffatomen, einen 5- bis 7-gliedrigen, gesättigten oder ungesättigten Heterocyclus mit bis zu 3 Heteroatomen aus der Reihe S, N oder O oder durch geradkettiges oder verzweigtes Alkyl mit bis zu 4 Kohlenstoffatomen substituiert ist, das seinerseits durch Aryl mit 6 bis 10 Kohlenstoffatomen substituiert sein kann,
• A eine direkte Bindung oder ein Sauerstoffatom bedeutet,
• R¹³ Wasserstoff oder Aryl mit 6 bis 10 Kohlenstoffatomen oder einen 5-bis 7- gliedrigen, gesättigten oder ungesättigten Heterocyclus mit bis zu 3 Heteroatomen aus der Reihe S, N oder O bedeutet, wobei die Cyclen gegebenenfalls bis zu 3-fach gleich oder verschieden durch Halogen, Cyano oder durch geradkettiges oder verzweigtes Alkyl, Alkoxy, Alkylthio, Alkoxycarbonyl, Halogenalkyl, Halogenalkoxy oder Halogenalkylthio mit jeweils bis zu 4 Kohlenstoffatomen substituiert sind, oder
  einen cyclischen, geradkettigen oder verzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 10 Kohlenstoffatomen bedeutet, der gegebenenfalls bis zu 3-fach gleich oder verschieden durch Sauerstoff oder durch - CO-, -CO-NH-, -O-CO-, -CO-O-, -NH-CO-, -S0₂-NH-, -NH-S0₂-, -S(0)_e-oder -N'^6- unterbrochen ist,
  worin
• e die oben angegebene Bedeutung von d hat und mit dieser gleich oder verschieden ist,
• R¹⁶ die oben angegebene Bedeutung von R¹⁵ hat und mit dieser gleich oder verschieden ist,
  oder der Kohlenwasserstoffrest gegebenenfalls bis zu 3-fach gleich oder verschieden durch Aryliden mit 6 bis 10 Kohlenstoffatomen oder heterocyclische Reste der Formeln
  
  
  unterbrochen ist,
  worin
• f und g gleich oder verschieden sind und eine Zahl 1 oder 2 bedeuten, und wobei Aryliden durch Halogen, Cyano oder durch geradkettiges oder verzweigtes Alkyl, Alkoxy, Alkylthio, Alkoxycarbonyl, Halogenalkyl, Halogenalkoxy oder Halogenalkylthio mit jeweils bis zu 4 Kohlenstoffatomen substituiert sein kann,
  und der Kohlenwasserstoffrest gegebenenfalls bis zu 3-fach gleich oder verschieden durch Cycloalkyl mit 3 bis 8 Kohlenstoffatomen, Halogen, Nitro, Cyano, Hydroxy, - O-N0₂, geradkettiges oder verzweigtes Alkylthio, Alkoxy oder Acyloxy mit jeweils bis zu 8 Kohlenstoffatomen oder durch Aryl, Aryloxy oder Arylthio mit jeweils 6 bis 10 Kohlenstoffatomen oder durch einen 5-bis 7-gliedrigen, gesättigten oder ungesättigen Heterocyclus mit bis zu 3 Heteroatomen aus der Reihe S, N oder O substituiert ist, wobei die Cyclen ihrerseits bis zu 3-fach gleich oder verschieden durch Halogen, Cyano oder durch geradkettiges oder verzweigtes Alkyl, Alkoxy, Alkylthio, Alkoxycarbonyl, Halogenalkyl, Halogenalkoxy oder Halogenalkylthio mit jeweils bis zu 4 Kohlenstoffatomen substituiert sein können, oder
  der Kohlenwasserstoffrest gegebenenfalls durch eine Gruppe der Formel -CO₂-R¹⁷, -CONR¹⁸R¹⁹, - NR²⁰R²¹, NH-S0₂-X und/oder -NR^22- C0₂ R²³ substituiert ist, worin
• R¹⁷ die oben angegebene Bedeutung von R¹⁵ hat und mit dieser gleich oder verschieden ist und
• R¹⁸, R¹⁹, R²⁰, R²¹, R²² und R²³ die oben angegebene Bedeutung von R¹¹ und R¹² haben und mit diesen gleich oder verschieden sind, und
• X Phenyl bedeutet, das gegebenenfalls durch Methyl substituiert ist,
• _R3 für Cyano, Nitro oder Formyl steht, oder
• R³ und R⁴ gemeinsam einen Rest der Formel
  
  bilden, worin
• E ein Sauerstoff-oder Schwefelatom oder die - CH₂-Gruppe bedeutet,
• R⁵ für einen cyclischen, geradkettigen oder verzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 12 Kohlenstoffatomen steht, der gegebenenfalls bis zu 2-fach gleich oder verschieden durch Sauerstoff oder Schwefel unterbrochen ist,
  und der gegebenenfalls bis zu 3-fach gleich oder verschieden durch Cycloalkyl mit 3 bis 8 Kohlenstoffatomen, geradkettiges oder verzweigtes Acyloxy mit bis zu 4 Kohlenstoffatomen, Halogen, Nitro, Cyano, Hydroxy oder durch Aryl, Aryloxy oder Arylthio mit jeweils 6 bis 10 Kohlenstoffatomen oder durch einen 5-bis 7-gliedrigen, gesättigten oder ungesättigen gegebenenfalls kondensierten Heterocyclus mit bis zu 5 Heteroatomen aus der Reihe S, N oder 0 substituiert ist, wobei die Cyclen ihrerseits bis zu 3-fach gleich oder verschieden durch Halogen, Cyano, Nitro, Hydroxy oder durch geradkettiges oder verzweigtes Alkyl oder Alkoxy mit jeweils bis zu 4 Kohlenstoffatomen, Trifluormethyl, Trifluormethoxy, Trifluormethylthio oder durch eine Gruppe der For- _mel - NR²⁴R²⁵ substituiert sein können, worin
• R²⁴ und R²⁵ die oben angegebene Bedeutung von R¹¹ und R¹² haben und mit dieser gleich oder verschieden sind,
  oder der Kohlenwasserstoffrest gegebenenfalls durch eine Gruppe der Formel -C0₂-R²⁶, CONR²7 _R ²⁸, - NR²⁹R³⁰,-NR³¹-CO₂R³² oder - NR^33-S0₂R³⁴ substituiert ist,
  worin
• _R ²⁶ die oben angegebene Bedeutung von R¹⁵ hat und mit dieser gleich oder verschieden ist und
• _R27, _R28, _R29, _R3⁰, _R3¹, _R3², R³³ und R³⁴ die oben angegebene Bedeutung von R¹¹ und R¹² haben und mit diesen gleich oder verschieden sind, oder
• R⁵ für einen 5-bis 7-gliedrigen, gesättigten oder ungesättigten Heterocyclus mit bis zu 4 Heteroatomen aus der Reihe S, N oder O steht, der gegebenenfalls bis zu 3-fach gleich oder verschieden durch Halogen, Amino, Cyano, Nitro oder durch geradkettiges oder verzweigtes Alkyl, Alkoxy, Alkylthio, Alkoxycarbonyl, Halogenalkyl, Halogenalkoxy oder Halogenalkylthio mit jeweils bis zu 4 Kohlenstoffatomen oder durch C1-C4-Mono- oder -Dialkylamino substituiert ist, oder
• R⁵ für eine Gruppe der Formel D-R³⁵ steht,
  worin
• D die CO- oder - S(O)_h-Gruppe oder ein Sauerstoffatom bedeutet,
  worin
• h eine Zahl 0, 1 oder 2 bedeutet, und
• _R3⁵ Aryl mit 6 bis 10 Kohlenstoffatomen oder einen 5-bis 7- gliedrigen, gesättigten oder ungesättigten Heterocyclus mit bis zu 3 Heteroatomen aus der Reihe S, N oder O bedeutet, die gegebenenfalls bis zu 3-fach gleich oder verschieden durch Halogen, Amino, Cyano, Nitro oder durch geradkettiges oder verzweigtes Alkyl, Alkoxy, Alkylthio, Alkoxycarbonyl, Halogenalkyl, Halogenalkoxy oder Halogenalkylthio mit jeweils bis zu 4 Kohlenstoffatomen oder durch C₁-C₄-Mono-oder - Dialkylamino substituiert sind, oder
• R³⁵ Wasserstoff oder einen cyclischen, geradkettigen oder verzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 8 Kohlenstoffatomen bedeutet, der gegebenenfalls durch Sauerstoff oder Schwefel unterbrochen ist, und der gegebenenfalls durch Halogen, Aryl, Aryloxy oder Arylthio mit jeweils 6 bis 10 Kohlenstoffatomen oder durch einen 5-bis 7-gliedrigen, gesättigten oder ungesättigen Heterocyclus mit bis zu 3 Heteroatomen aus der Reihe S, N oder O substituiert ist, wobei die Cyclen ihrerseits durch Halogen, Trifluormethyl, Methyl, Methoxy, Nitro oder Methylthio substituiert sein können, oder
  durch eine Gruppe der Formel - NR36R37 substituiert ist worin
• R³⁶ und R³⁷ die oben angegebene Bedeutung von R¹¹ und R¹² haben und mit dieser gleich oder verschieden sind,
  und deren Salze,
  mit der Maßgabe, daß R⁵ nicht für gegebenenfalls halogensubstituiertes Pyridyl oder Thienyl stehen darf.

The present invention relates to new 3-quinolyl-substituted dihydropyridines of the general formula (I)

in which

• R ¹ and R ^{4 are} identical or different and represent hydrogen, amino, cyano, formyl, trifluoromethyl or straight-chain or branched alkyl having up to 8 carbon atoms, which may be substituted by hydroxyl or by a group of the formula -NR ⁶ R ⁷ , - O-CO-R ⁸ , -O- (CH ₂ ) _a -OR ^{8 '} or -0- (CH ₂ ) _b -NR ⁹ R' ^{0 is} substituted, wherein
• R ⁶ , R ⁷ , R ⁹ and R ^{10 are} identical or different and denote hydrogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms,
• R ⁸ and R ⁸ 'are identical or different and denote straight-chain or branched alkyl having up to 6 carbon atoms, and
• a and b are the same or different and represent a number 2, 3, 4 or 5,
• R ^{2 represents} a group of the formula - CO-NR ¹¹ R ¹² or -CO-AR ¹³ , wherein
• R ¹¹ and R ^{12 are the} same or different and are hydrogen, a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical with up to 8 carbon atoms, which may be halogen, hydroxy, cyano or aryl, aryloxy, arylthio with 6 to 10 each Carbon atoms or by a 5- to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O is substituted, the cycles in turn by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, Alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio, each with up to 4 carbon atoms, or aryl with 6 to 10 carbon atoms or a 5- to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O mean, optionally up to 2 times the same or different by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 4 carbon atoms, or
• R ¹¹ and R ¹² together, including the nitrogen atom, form a 3 to 8-membered, saturated or unsaturated heterocycle which is optionally interrupted by an oxygen atom or by a radical of the formula S (O) _d , -CO- or -NR ¹⁵ can be what
• d represents a number 0, 1 or 2,
• R ^{15 is} hydrogen or aryl having 6 to 10 carbon atoms, optionally up to 2 times the same or different by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio alkoxycarbonyl each having up to 8 carbon atoms, haloalkyl, haloalkoxy or haloalkylthio in each case up to 4 carbon atoms is substituted, or
  represents a cyclic, saturated or unsaturated, straight-chain or branched hydrocarbon radical having up to 8 carbon atoms, which may be by hydroxyl, halogen or aryl having 6 to 10 carbon atoms or a 5 to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms from the series S, N or O is substituted, the cycles themselves being up to 2 times identical or different by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio, each with up to 4 Carbon atoms can be substituted,
  and the heterocycle optionally by straight-chain or branched alkoxy or alkylthio each having up to 4 carbon atoms, halogen, aryl having 6 to 10 carbon atoms, a 5- to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms from the series S, N or O or is substituted by straight-chain or branched alkyl having up to 4 carbon atoms, which in turn can be substituted by aryl having 6 to 10 carbon atoms,
• A represents a direct bond or an oxygen atom,
• R ¹³ denotes hydrogen or aryl having 6 to 10 carbon atoms or a 5 to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O, the cycles optionally being up to 3 times identical or different are substituted by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 4 carbon atoms, or
  is a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical having up to 10 carbon atoms, which may be up to 3 times the same or different by oxygen or by - CO-, -CO-NH-, -O-CO-, -CO -O-, -NH-CO-, -S0 ₂ -NH-, -NH-S0 ₂ -, -S (0) _e -or -N ' ^{6- is} interrupted,
  wherein
• e has the meaning of d given above and is the same or different with it,
• R ^{16 has} the meaning of R ¹⁵ given above and is the same or different with it,
  or the hydrocarbon radical optionally up to 3 times the same or different by arylidene having 6 to 10 carbon atoms or heterocyclic radicals of the formulas
  
  
  is interrupted
  wherein
• f and g are the same or different and represent a number 1 or 2, and wherein arylidene by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, halogen nalkyl, haloalkoxy or haloalkylthio, each having up to 4 carbon atoms, can be substituted,
  and the hydrocarbon radical optionally up to 3 times the same or different by cycloalkyl having 3 to 8 carbon atoms, halogen, nitro, cyano, hydroxy, - O-N0 ₂ , straight-chain or branched alkylthio, alkoxy or acyloxy each having up to 8 carbon atoms or by Aryl, aryloxy or arylthio each having 6 to 10 carbon atoms or by a 5 to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O is substituted, the cycles in turn up to 3 times may be substituted, identically or differently, by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio, each having up to 4 carbon atoms, or
  the hydrocarbon radical is optionally substituted by a group of the formula -CO ₂ -R ¹⁷ , -CONR ¹⁸ R ¹⁹ , - NR ²⁰ R ²¹ , NH-S0 ₂ -X and / or -NR ^22- C0 ₂ R ²³ , wherein
• R ^{17 has} the meaning of R ¹⁵ given above and is the same or different with it and
• R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² and R ^{23 have} the abovementioned meaning of R ¹¹ and R ¹² and are the same or different with these, and
• X denotes phenyl which is optionally substituted by methyl,
• _R 3 represents cyano, nitro or formyl, or
• R ³ and R ⁴ together represent a radical of the formula
  
  form what
• E represents an oxygen or sulfur atom or the --CH ₂ group,
• R ^{5 represents} a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical with up to 12 carbon atoms, which is optionally interrupted up to 2 times by the same or different means by oxygen or sulfur,
  and optionally up to 3 times the same or different by cycloalkyl having 3 to 8 carbon atoms, straight-chain or branched acyloxy having up to 4 carbon atoms, halogen, nitro, cyano, hydroxy or by aryl, aryloxy or arylthio each having 6 to 10 carbon atoms or is substituted by a 5- to 7-membered, saturated or unsaturated, optionally condensed heterocycle with up to 5 heteroatoms from the series S, N or 0, the cycles themselves being up to 3 times identical or different by halogen, cyano, nitro, Hydroxy or by straight-chain or branched alkyl or alkoxy each having up to 4 carbon atoms, trifluoromethyl, trifluoromethoxy, trifluoromethylthio or by a group of the _mel - NR ²⁴ R ²⁵ can be substituted, wherein
• R ²⁴ and R ^{25 have} the meaning of R ¹¹ and R ¹² given above and are the same or different with this,
  or the hydrocarbon radical is optionally substituted by a group of the formula -C0 ₂ -R ²⁶ , CONR ² 7 _R ²⁸ , - NR ²⁹ R ³⁰ , -NR ³¹ -CO ₂ R ³² or - NR ^33- S0 ₂ R ³⁴ ,
  wherein
• _R ^{26 has} the meaning of R ¹⁵ given above and is the same or different with it and
• _R 27, _R 28, _R 29, _R 3 ⁰ , _R 3 ¹ , _R 3 ² , R ³³ and R ^{34 have} the meaning given above of R ¹¹ and R ¹² and are the same or different with them, or
• R ^{5 represents} a 5- to 7-membered, saturated or unsaturated heterocycle with up to 4 heteroatoms from the series S, N or O, which may be up to 3 times identical or different by halogen, amino, cyano, nitro or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 4 carbon atoms or substituted by C1-C4-mono- or -dialkylamino, or
• R ^{5 represents} a group of the formula DR ³⁵ ,
  wherein
• D represents the CO or S (O) _h group or an oxygen atom,
  wherein
• h represents a number 0, 1 or 2, and
• _R 3 ⁵ is aryl having 6 to 10 carbon atoms or a 5-to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms from the series S, N or O, which are optionally substituted up to 3 times in an identical or different manner by halogen, Amino, cyano, nitro or are substituted by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 4 carbon atoms or by C ₁ -C ₄ mono-or - dialkylamino, or
• R ^{35 is} hydrogen or a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms, which is optionally interrupted by oxygen or sulfur, and which is optionally halogen, aryl, aryloxy or arylthio, each having 6 to 10 carbon atoms or by a 5 to 7-membered, saturated or unsaturated heterocycle is substituted with up to 3 heteroatoms from the series S, N or O, where the cycles in turn can be substituted by halogen, trifluoromethyl, methyl, methoxy, nitro or methylthio, or
  is substituted by a group of the formula - NR36R37 wherein
• R ³⁶ and R ^{37 have} the meaning of R ¹¹ and R ¹² given above and are the same or different with this,
  and their salts,
  with the proviso that R ^{5 may} not represent optionally halogen-substituted pyridyl or thienyl.

Physiologically acceptable salts can be salts of the compounds according to the invention with inorganic or organic acids. Salts with inorganic acids such as, for example, hydrochloric acid, hydrobromic acid, phosphoric acid or sulfuric acid, or salts with organic carboxylic or sulfonic acids such as, for example, acetic acid, maleic acid, fumaric acid, malic acid, citric acid, tartaric acid, lactic acid, benzoic acid, or methanesulfonic acid, ethanesulfonic acid, phenylsulfonic acid, toluene sulfonic acid, are preferred or naphthalenedisulfonic acid.

The compounds according to the invention exist in stereoisomeric forms which either behave like images and mirror images (enantiomers) or do not behave like images and mirror images (diastereomers). The invention relates to both the antipodes and the racemic forms as well as the diastereomer mixtures. The racemic forms, like the diastereomers, can be separated into the stereoisomerically uniform constituents in a known manner (cf. E.L. Eliel, Stereochemistry of Carbon Compounds, McGraw Hill, 1962).

• R¹ und R⁴ gleich oder verschieden sind und für Wasserstoff, Amino, Cyano, Formyl, Trifluormethyl oder für geradkettiges oder verzweigtes Alkyl mit bis zu 4 Kohlenstoffatomen stehen, das gegebenenfalls durch Hydroxy, durch eine Gruppe der Formel -NR6 R7, -O-CO-R⁸, -O-(CH₂)_a-OR^8' oder -O-(CH₂)_b,-NR⁹R¹⁰ substituiert ist, worin
• R⁶, R⁷, R⁹ und R¹⁰ gleich oder verschieden sind und Wasserstoff oder geradkettiges oder verzweigtes Alkyl mit bis zu 4 Kohlenstoffatomen bedeuten,
• R⁸ und R⁸' gleich oder verschieden sind und geradkettiges oder verzweigtes Alkyl mit bis zu 4 Kohlenstoffatomen bedeuten, und
• a und b gleich oder verschieden sind und eine Zahl 2, 3, 4 oder 5 bedeuten,
• R² für eine Gruppe der Formel - CO-NR¹¹R¹² oder -CO-A-R¹³ steht, worin
• R11 und R¹² gleich oder verschieden sind und Wasserstoff, einen geradkettigen, verzweigten oder cyclischen, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 6 Kohlenstoffatomen bedeuten, der gegebenenfalls durch Fluor, Chlor, Hydroxy, Phenyl oder Pyridyl substituiert ist, wobei die Cyclen ihrerseits durch Fluor, Chlor oder durch Alkyl, Alkoxy, Alkylthio oder Alkoxycarbonyl mit jeweils bis zu 2 Kohlenstoffatomen, Trifluormethyl oder Trifluormethoxy substituiert sein können, oder
  Phenyl oder Pyridyl bedeuten, die gegebenenfalls durch Fluor, Chlor oder durch Alkyl, Alkoxy, Alkylthio oder Alkoxycarbonyl mit jeweils bis zu 2 Kohlenstoffatomen, Trifluormethyl oder Trifluormethoxy substituiert sind, oder
• R¹¹ und R¹² gemeinsam unter Einbezug des Stickstoffatoms einen 3-bis 8-gliedrigen, gesättigen oder ungesättigten Heterocyclus bilden, der gegebenenfalls durch ein Sauerstoffatom oder durch einen Rest der Formel S(O)_d, -CO- oder -NR¹⁵ unterbrochen sein kann, worin
• d eine Zahl 0, 1 oder 2 bedeutet,
• R¹⁵ Wasserstoff oder Phenyl bedeutet, das gegebenenfalls durch Fluor, Chlor, Methyl, Ethyl, Methoxy, Ethoxy, Trifluormethyl oder Trifluormethoxy substituiert ist, oder einen cyclischen, gesättigten oder ungesättigten, geradkettigen oder verzweigten Kohlenwasserstoffrest mit bis zu 4 Kohlenstoffatomen bedeutet, der gegebenenfalls durch Fluor, Chlor, Phenyl oder durch einen 5-bis 7-gliedrigen, gesättigten oder ungesättigten Heterocyclus mit bis zu 3 Heteroatomen aus der Reihe S, N oder O substituiert ist, wobei die Cyclen ihrerseits durch Fluor, Chlor, Methyl, Methoxy, Methylthio, Trifluormethyl oder Trifluormethoxy substituiert sein können,
• A eine direkte Bindung oder ein Sauerstoffatom bedeutet,
• R¹³ Wasserstoff, Phenyl oder Pyridyl bedeutet, die gegebenenfalls durch Fluor, Chlor, Methyl, Methoxy, Methylthio, Trifluormethyl oder Trifluormethoxy substituiert sind, oder
  einen cyclischen, geradkettigen oder verzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 8 Kohlenstoffatomen bedeutet, der gegebenenfalls bis zu 2-fach gleich oder verschieden durch Sauerstoff oder durch - CO-, -CO-NH-, -O-CO-, -CO-O-, -NH-CO-, -S0₂-NH-, -NH-S0₂-, -S(O)_e-oder -NR¹⁶- unterbrochen ist, worin
• e die oben angegebene Bedeutung von d hat und mit dieser gleich oder verschieden ist,
• R¹⁶ die oben angegebene Bedeutung von R¹⁵ hat und mit dieser gleich oder verschieden ist,
  oder der Kohlenwasserstoffrest gegebenenfalls bis zu 2-fach gleich oder verschieden durch Aryliden mit 6 bis 10 Kohlenstoffatomen oder heterocyclische Reste der Formeln
  
  
  unterbrochen ist,
  worin
• f und g gleich oder verschieden sind und eine Zahl 1 oder 2 bedeuten, und der Kohlenwasserstoffrest gegebenenfalls bis zu 2-fach gleich oder verschieden durch Cyclopropyl, Cyclobutyl, Cyclopentyl, Cyclohexyl, Fluor, Chlor, Nitro, Cyano, Hydroxy, - O-N0₂, geradkettiges oder verzweigtes Alkylthio, Alkoxy oder Acyloxy mit jeweils bis zu 4 Kohlenstoffatomen oder durch Phenyl, Phenoxy, Phenylthio oder Pyridyl substituiert ist, wobei die Cyclen ihrerseits durch Fluor, Chlor, Cyano, Methyl, Methoxy, Methylthio, Trifluormethyl oder Trifluormethoxy substituiert sein können, oder
  der Kohlenwasserstofftest gegebenenfalls durch eine Gruppe der Formel -CO₂-R¹⁷, -CONR¹⁸R¹⁹, - NR²⁰R²¹, -NH-S0₂-X und/oder -NR^22- CO₂R²³ substituiert ist, worin
• R¹⁷ die oben angegebene Bedeutung von R¹⁵ hat und mit dieser gleich oder verschieden ist und
• R¹⁸, R¹⁹, R²⁰, R²¹, R²² und R²³ die oben angegebene Bedeutung von R¹¹ und R¹² haben und mit diesen gleich oder verschieden sind, und
• X Phenyl bedeutet, das gegebenenfalls durch Methyl substituiert ist,
• _R3 für Cyano, Nitro oder Formyl steht,
  oder
• R³ und R⁴ gemeinsam einen Rest der Formel
  
  
  bilden,
  worin
• E ein Sauerstoff-oder Schwefelatom oder die - CH₂-Gruppe bedeutet,
• R⁵ für einen cyclischen, geradkettigen oder verzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 10 Kohlenstoffatomen steht, der gegebenenfalls durch Sauerstoff oder Schwefel unterbrochen ist,
  und der gegebenenfalls bis zu 2-fach gleich oder verschieden durch Cyclopropyl, Cyclobutyl, Cyclopentyl, Cyclohexyl, Fluor, Chlor, Brom, Acyloxy mit bis zu 2 Kohlenstoffatomen, Cyano, Hydroxy oder durch Phenyl, Phenyloxy, Phenylthio oder durch einen 5-bis 7-gliedrigen, gesättigten oder ungesättigen Heterocyclus mit bis zu 3 Heteroatomen aus der Reihe S, N oder O substituiert ist, wobei die Phenyl-und die Hetero-Cyclen ihrerseits bis zu 2-fach gleich oder verschieden durch Fluor, Chlor, Brom, Hydroxy, Methyl, Ethyl, Methoxy, Ethoxy, Trifluormethyl, Trifluormethoxy oder Trifluormethylthio oder durch eine Gruppe der Formel - NR²⁴ _R ²⁵ substituiert sein können,
  worin
• R²⁴ und R²⁵ die oben angegebene Bedeutung von R¹¹ und R¹² haben und mit dieser gleich oder verschieden sind,
  oder der Kohlenwasserstoffrest gegebenenfalls durch eine Gruppe der Formel -C0₂-R²⁶, - CONR27 R28, - _NR29_R30, - NR³¹-CO²R³² oder - NR^33-S0₂R³⁴ substituiert ist,
  worin
• _R ²⁶ die oben angegebene Bedeutung von R¹⁵ hat und mit dieser gleich oder verschieden ist und
• _R27, _R28, _R29, _R30, _R3¹, _R3², _R33 und R³⁴ die oben angegebene Bedeutung von R¹¹ und R¹² haben und mit diesen gleich oder verschieden sind, oder
• R⁵ für einen 5-bis 7-gliedrigen, gesättigten oder ungesättigten Heterocyclus mit bis zu 4 Heteroatomen aus der Reihe S, N oder O steht, der gegebenenfalls bis zu 2-fach gleich oder verschieden durch Fluor, Chlor, Brom, Cyano, Nitro oder durch Alkyl, Alkoxy, Alkylthio, Alkoxycarbonyl, Halogenalkyl, Halogenalkoxy oder Halogenalkylthio mit jeweils bis zu 2 Kohlenstoffatomen, Amino oder durch C1-C4-Mono- oder - Dialkylamino substituiert ist, oder
• R⁵ für eine Gruppe der Formel D-R³⁵ steht, worin
• D die CO- oder - S(O)_h-Gruppe oder ein Sauerstoffatom bedeutet, worin
• h eine Zahl 0, 1 oder 2 bedeutet, und
• R³⁵ Phenyl oder einen 5-bis 7-gliedrigen, gesättigten oder ungesättigten Heterocyclus mit bis zu 3 Heteroatomen aus der Reihe S, N oder O bedeutet, die gegebenenfalls bis zu 2- fach gleich oder verschieden durch Fluor, Chlor, Brom, Cyano, Nitro oder durch geradkettiges oder verzweigtes Alkyl, Alkoxy, Alkylthio, Alkoxycarbonyl, Halogenalkyl, Halogenalkoxy oder Halogenalkylthio mit jeweils bis zu 4 Kohlenstoffatomen, Amino oder durch C1-C4-Mono- oder -Dialkylamino substituiert sind, oder
• _R ³⁵ Wasserstoff oder einen cyclischen, geradkettigen oder verzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 8 Kohlenstoffatomen bedeutet, der gegebenenfalls durch Sauerstoff oder Schwefel unterbrochen ist, und der gegebenenfalls durch Fluor, Chlor, Phenyl, Phenoxy oder Phenylthio substituiert sein kann, oder durch eine Gruppe der Formel - NR36R37 substituiert ist worin
• R³⁶ und R³⁷ die oben angegebene Bedeutung von R¹¹ und R¹² haben und mit dieser gleich oder verschieden sind,
  und deren Salze,
  mit der Maßgabe, daß R⁵ nicht für gegebenenfalls halogensubstituiertes Pyridyl oder Thienyl stehen darf.

Compounds of the general formula (I) in which

• R ¹ and R ^{4 are} identical or different and represent hydrogen, amino, cyano, formyl, trifluoromethyl or straight-chain or branched alkyl having up to 4 carbon atoms, which may be replaced by hydroxyl, by a group of the formula -NR6 R7, -O- CO-R ⁸ , -O- (CH ₂ ) _a -OR ^{8 '} or -O- (CH ₂ ) _b , -NR ⁹ R ^{10 is} substituted, wherein
• R ⁶ , R ⁷ , R ⁹ and R ^{10 are} identical or different and denote hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms,
• R ⁸ and R ⁸ 'are identical or different and represent straight-chain or branched alkyl having up to 4 carbon atoms, and
• a and b are the same or different and represent a number 2, 3, 4 or 5,
• R ^{2 represents} a group of the formula - CO-NR ¹¹ R ¹² or -CO-AR ¹³ , wherein
• R11 and R ^{12 are the} same or different and are hydrogen, a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical having up to 6 carbon atoms, which is optionally substituted by fluorine, chlorine, hydroxy, phenyl or pyridyl, the cycles in turn being fluorine , Chlorine or substituted by alkyl, alkoxy, alkylthio or alkoxycarbonyl each having up to 2 carbon atoms, trifluoromethyl or trifluoromethoxy, or
  Phenyl or pyridyl, which are optionally substituted by fluorine, chlorine or by alkyl, alkoxy, alkylthio or alkoxycarbonyl each having up to 2 carbon atoms, trifluoromethyl or trifluoromethoxy, or
• R ¹¹ and R ¹² together, including the nitrogen atom, form a 3 to 8-membered, saturated or unsaturated heterocycle which may be interrupted by an oxygen atom or by a radical of the formula S (O) _d , -CO- or -NR ¹⁵ can in what
• d represents a number 0, 1 or 2,
• R ^{15 is} hydrogen or phenyl, which is optionally substituted by fluorine, chlorine, methyl, ethyl, methoxy, ethoxy, trifluoromethyl or trifluoromethoxy, or a cyclic, saturated or unsaturated, straight-chain or branched hydrocarbon radical having up to 4 carbon atoms, which is optionally substituted by Fluorine, chlorine, phenyl or by a 5- to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O is substituted, the cycles being themselves fluorine, chlorine, methyl, methoxy, methylthio, Trifluoromethyl or trifluoromethoxy can be substituted,
• A represents a direct bond or an oxygen atom,
• R ¹³ denotes hydrogen, phenyl or pyridyl, which are optionally substituted by fluorine, chlorine, methyl, methoxy, methylthio, trifluoromethyl or trifluoromethoxy, or
  represents a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms, the given if up to 2 times the same or different by oxygen or by - CO-, -CO-NH-, -O-CO-, -CO-O-, -NH-CO-, -S0 ₂ -NH-, -NH -S0 ₂ -, -S (O) _e -or -NR ¹⁶ - is interrupted, wherein
• e has the meaning of d given above and is the same or different with it,
• R ^{16 has} the meaning of R ¹⁵ given above and is the same or different with it,
  or the hydrocarbon radical optionally up to 2 times the same or different by arylidene having 6 to 10 carbon atoms or heterocyclic radicals of the formulas
  
  
  is interrupted
  wherein
• f and g are the same or different and represent a number 1 or 2, and the hydrocarbon radical optionally up to 2 times the same or different by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, fluorine, chlorine, nitro, cyano, hydroxy, - O-N0 ₂ , straight-chain or branched alkylthio, alkoxy or acyloxy each having up to 4 carbon atoms or substituted by phenyl, phenoxy, phenylthio or pyridyl, the cycles in turn being substituted by fluorine, chlorine, cyano, methyl, methoxy, methylthio, trifluoromethyl or trifluoromethoxy can, or
  the hydrocarbon test is optionally substituted by a group of the formula -CO ₂ -R ¹⁷ , -CONR ¹⁸ R ¹⁹ , - NR ²⁰ R ²¹ , -NH-S0 ₂ -X and / or -NR ^22- CO ₂ R ²³ , wherein
• R ^{17 has} the meaning of R ¹⁵ given above and is the same or different with it and
• R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² and R ^{23 have} the abovementioned meaning of R ¹¹ and R ¹² and are the same or different with these, and
• X denotes phenyl which is optionally substituted by methyl,
• _R 3 represents cyano, nitro or formyl,
  or
• R ³ and R ⁴ together represent a radical of the formula
  
  
  form,
  wherein
• E represents an oxygen or sulfur atom or the --CH ₂ group,
• R ⁵ for a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical with up to 10 Carbon atoms, which may be interrupted by oxygen or sulfur,
  and optionally up to 2 times the same or different by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, fluorine, chlorine, bromine, acyloxy having up to 2 carbon atoms, cyano, hydroxy or by phenyl, phenyloxy, phenylthio or by a 5 to 7 -linked, saturated or unsaturated heterocycle is substituted with up to 3 heteroatoms from the series S, N or O, the phenyl and heterocycles in turn being up to 2 times identical or different by fluorine, chlorine, bromine, hydroxyl, Methyl, ethyl, methoxy, ethoxy, trifluoromethyl, trifluoromethoxy or trifluoromethylthio or can be substituted by a group of the formula - NR ²⁴ _R ²⁵ ,
  wherein
• R ²⁴ and R ^{25 have} the meaning of R ¹¹ and R ¹² given above and are the same or different with this,
  or the hydrocarbon radical is optionally substituted by a group of the formula -C0 ₂ -R ²⁶ , - CONR27 R28, - _NR 29 _R 30, - NR ³¹ -CO ² R ³² or - NR ^33- S0 ₂ R ³⁴ ,
  wherein
• _R ^{26 has} the meaning of R ¹⁵ given above and is the same or different with it and
• _R 27, _R 28, _R 29, _R 30, _R 3 ¹ , _R 3 ² , _R 33 and R ^{34 have} the meaning given above of R ¹¹ and R ¹² and are the same or different with them, or
• R ^{5 represents} a 5 to 7-membered, saturated or unsaturated heterocycle with up to 4 heteroatoms from the series S, N or O, which may be up to 2 times identical or different due to fluorine, chlorine, bromine, cyano, nitro or is substituted by alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 2 carbon atoms, amino or by C1-C4-mono- or dialkylamino, or
• R ^{5 represents} a group of the formula DR ³⁵ , in which
• D represents the CO or S (O) _h group or an oxygen atom, wherein
• h represents a number 0, 1 or 2, and
• R ^{35 is} phenyl or a 5- to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O, which may be up to 2 times identical or different from fluorine, chlorine, bromine, cyano, Nitro or substituted by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 4 carbon atoms, amino or by C1-C4-mono- or -dialkylamino, or
• _R ^{35 is} hydrogen or a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical with up to 8 carbon atoms, which is optionally interrupted by oxygen or sulfur, and which is optionally by fluorine, chlorine, phenyl, phenoxy or phenylthio, or substituted by a group of the formula - NR36R37 wherein
• R ³⁶ and R ^{37 have} the meaning of R ¹¹ and R ¹² given above and are the same or different with this,
  and their salts,
  with the proviso that R ^{5 may} not represent optionally halogen-substituted pyridyl or thienyl.

• R¹ und R⁴ gleich oder verschieden sind und für Wasserstoff, Amino, Trifluormethyl, Methyl oder Ethyl stehen,
• R² für eine Gruppe der Formel -CO-NR¹¹R¹² oder -CO-A-R¹³ steht, worin
• R¹¹ und R¹² gleich oder verschieden sind und Wasserstoff, einen geradkettigen, verzweigten oder cyclischen, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 6 Kohlenstoffatomen bedeuten, oder Phenyl bedeuten, das gegebenenfalls durch Fluor, Chlor, Methyl oder Methoxy substituiert ist,
• A eine direkte Bindung oder ein Sauerstoffatom bedeutet,
• R¹³ Wasserstoff oder einen cyclischen, geradkettigen oder verzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 8 Kohlenstoffatomen bedeutet, der gegebenenfalls durch Sauerstoff oder Schwefel oder durch -CO-NH-, -O-CO-, -CO-O-, -NH-CO-, -S0₂-NH-, -NH-S0₂- oder -NR'^6- unterbrochen ist, worin
• R¹⁶ Wasserstoff, geradkettiges oder verzweigtes Alkyl mit bis zu 4 Kohlenstoffatomen bedeutet,
  oder der Kohlenwasserstoffrest durch heterocyclische Reste der Formeln
  
  
  unterbrochen ist, worin
• f und g gleich oder verschieden sind und eine Zahl 1 oder 2 bedeuten, und der Kohlenwasserstoffrest gegebenenfalls durch Cyclopropyl, Cyclobutyl, Cyclopentyl, Cyclohexyl, Fluor, Chlor, Nitro, Cyano, Hydroxy oder durch Phenyl, Phenoxy, Phenylthio oder Pyridyl substituiert ist, die ihrerseits durch Fluor, Chlor, Methyl, Methoxy, Methylthio, Trifluormethyl oder Trifluormethoxy substituiert sein können, oder der Kohlenwasserstoffrest gegebenenfalls durch eine Gruppe der Formel -C0₂R¹⁷, -CONR¹⁸R¹⁹, -NR²⁰R²¹, - NH-S0₂-X und/oder -NR^22-C0₂R²³ substituiert ist, worin
• R²⁰ und R²¹ gleich oder verschieden sind und Wasserstoff, einen geradkettigen, verzweigten oder cyclischen, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 6 Kohlenstoffatomen bedeuten, das gegebenenfalls durch Fluor, Chlor, Pyridyl oder Phenyl substituiert ist, das seinerseits durch Fluor, Chlor, Methyl oder Methoxy substituiert sein kann, oder Phenyl bedeuten, das gegebenenfalls durch Fluor, Chlor, Methyl oder Methoxy substituiert ist, oder
• R²⁰ und R²¹ gemeinsam unter Einbezug des Stickstoffatoms einen 5-bis 6-gliedrigen, gesättigen oder ungesättigten Heterocyclus bilden, der gegebenenfalls bis zu 2 weitere Heteroatome aus der Reihe S, N oder O enthalten kann und der gegebenenfalls auch geradkettiges oder verzweigtes Alkyl mit bis zu 4 Kohlenstoffatomen, Benzyl oder Phenyl substituiert ist,
• X Phenyl bedeutet, das gegebenenfalls durch Methyl substituiert ist,
• R¹⁷, R¹⁸, R¹⁹, R²² und R²³ gleich oder verschieden sind und Wasserstoff, geradkettiges oder verzweigtes Alkyl mit bis zu 6 Kohlenstoffatomen bedeuten, das gegebenenfalls durch Phenyl substituiert ist, oder Phenyl bedeuten, das gegebenenfalls durch Fluor, Chlor oder Brom substituiert ist,
• _R3 für Cyano, Nitro oder Formyl steht,
  oder
• R³ und R⁴ gemeinsam einen Rest der Formel
  
  
  bilden,
  worin
• E ein Sauerstoff-oder Schwefelatom oder die - CH₂-Gruppe bedeutet,
• R⁵ für einen cyclischen, geradkettigen oder verzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 8 Kohlenstoffatomen steht, der gegebenenfalls durch Sauerstoff oder Schwefel unterbrochen ist,
  und der gegebenenfalls durch Cyclopropyl, Cyclobutyl, Cyclopentyl, Cyclohexyl, Fluor, Chlor, Nitro, Cyano, Hydroxy oder durch Phenyl, Phenyloxy, Phenylthio oder durch einen 5-bis 7-gliedrigen, gesättigten oder ungesättigen Heterocyclus mit bis zu 2 Heteroatomen aus der Reihe S, N oder O substituiert ist, wobei die Phenyl-und die Hetero-Cyclen ihrerseits bis zu 2-fach gleich oder verschieden durch Fluor, Chlor, Methyl, Methoxy, Trifluormethyl oder Trifluormethoxy oder durch eine Gruppe der Formel -NR²⁴R²⁵ substituiert sein können, worin
• R²⁴ und R²⁵ die oben angegebene Bedeutung von R¹¹ und R¹² haben und mit dieser gleich oder verschieden sind,
  oder der Kohlenwasserstoffrest gegebenenfalls durch eine Gruppe der Formel -C0₂-R²⁶, - CONR27 R28, - _NR29_R30, - NR³¹-CO₂R³² oder - NR^33-S0₂R³⁴ substituiert ist, worin
• _R ²⁶ Alkyl mit 1-4 C-Atomen oder Phenyl bedeutet, und
• _R27, _R28, _R29, _R30, _R3¹, _R3², _R33 und R³⁴ die oben angegebene Bedeutung von R¹¹ und R¹² haben und mit diesen gleich oder verschieden sind, oder
• R⁵ für einen 5-bis 6-gliedrigen, gesättigten oder ungesättigten Heterocyclus mit bis zu 2 Heteroatomen aus der Reihe S, N oder O steht, der gegebenenfalls durch Fluor, Chlor, Methyl, Methoxy, Methylthio oder Trifluormethyl substituiert ist, oder
• R⁵ für eine Gruppe der Formel D-R³⁵ steht, worin
• D die -S(O)_h-Gruppe oder ein Sauerstoffatom bedeutet, worin
• h eine Zahl 0, 1 oder 2 bedeutet, und
• R³⁵ Phenyl bedeutet, das gegebenenfalls durch Fluor, Chlor, Brom, Methyl, Methoxy, Methylthio,Trifluormethyl, Amino oder durch C₁-C₂-Mono- oder - Dialkylamino substituiert ist, oder
• _R ³⁵ Wasserstoff, einen cyclischen, geradkettigen oder verzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 6 Kohlenstoffatomen bedeutet, der gegebenenfalls durch Sauerstoff oder Schwefel unterbrochen ist, und der gegebenenfalls durch Fluor, Chlor oder Phenyl substituiert ist, oder
  durch eine Gruppe der Formel - NR36R37 substituiert ist worin
• R³⁶ und R³⁷ die oben angegebene Bedeutung von R¹¹ und R¹² haben und mit dieser gleich oder verschieden sind,

und deren Salze,
mit der Maßgabe, daß R⁵ nicht für gegebenenfalls halogensubstituiertes Pyridyl oder Thienyl stehen darf.Compounds of the general formula (I) in which

• R ¹ and R ^{4 are the} same or different and represent hydrogen, amino, trifluoromethyl, methyl or ethyl,
• R ^{2 represents} a group of the formula -CO-NR ¹¹ R ¹² or -CO-AR ¹³ , wherein
• R ¹¹ and R ^{12 are the} same or different and are hydrogen, a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical having up to 6 carbon atoms, or are phenyl which is optionally substituted by fluorine, chlorine, methyl or methoxy,
• A represents a direct bond or an oxygen atom,
• R ^{13 is} hydrogen or a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms, which may be by oxygen or sulfur or by -CO-NH-, -O-CO-, -CO-O-, -NH -CO-, -S0 ₂ -NH-, -NH-S0 ₂ - or -NR ' ^{6- is} interrupted, wherein
• R ¹⁶ denotes hydrogen, straight-chain or branched alkyl having up to 4 carbon atoms,
  or the hydrocarbon radical by heterocyclic radicals of the formulas
  
  
  is interrupted in what
• f and g are the same or different and represent a number 1 or 2, and the hydrocarbon radical is optionally substituted by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, fluorine, chlorine, nitro, cyano, hydroxy or by phenyl, phenoxy, phenylthio or pyridyl, which in turn can be substituted by fluorine, chlorine, methyl, methoxy, methylthio, trifluoromethyl or trifluoromethoxy, or the hydrocarbon radical optionally by a group of the formula -C0 ₂ R ¹⁷ , -CONR ¹⁸ R ¹⁹ , -NR ²⁰ R ²¹ , - NH-S0 ₂ -X and / or -NR ^22- C0 ₂ R ^{23 is} substituted, wherein
• R ²⁰ and R ^{21 are} identical or different and are hydrogen, a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical having up to 6 carbon atoms, which is optionally substituted by fluorine, chlorine, pyridyl or phenyl, which in turn is substituted by fluorine, chlorine, Methyl or methoxy may be substituted, or phenyl, which is optionally substituted by fluorine, chlorine, methyl or methoxy, or
• R ²⁰ and R ²¹ together, including the nitrogen atom, form a 5 to 6-membered, saturated or unsaturated heterocycle which can optionally contain up to 2 further heteroatoms from the S, N or O series and which is optionally also substituted by straight-chain or branched alkyl having up to 4 carbon atoms, benzyl or phenyl,
• X denotes phenyl which is optionally substituted by methyl,
• R ¹⁷ , R ¹⁸ , R ¹⁹ , R ²² and R ^{23 are the} same or different and are hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, which is optionally substituted by phenyl, or phenyl, which is optionally substituted by fluorine, chlorine or Bromine is substituted,
• _R 3 represents cyano, nitro or formyl,
  or
• R ³ and R ⁴ together represent a radical of the formula
  
  
  form,
  wherein
• E represents an oxygen or sulfur atom or the --CH ₂ group,
• R ^{5 represents} a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical with up to 8 carbon atoms, which is optionally interrupted by oxygen or sulfur,
  and optionally by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, fluorine, chlorine, nitro, cyano, hydroxy or by phenyl, phenyloxy, phenylthio or by a 5 to 7-membered, saturated or unsaturated heterocycle with up to 2 heteroatoms from the series S, N or O is substituted, the phenyl and the heterocycles in turn being substituted up to 2 times, identically or differently, by fluorine, chlorine, methyl, methoxy, trifluoromethyl or trifluoromethoxy or by a group of the formula -NR ²⁴ R ²⁵ can be what
• R ²⁴ and R ^{25 have} the meaning of R ¹¹ and R ¹² given above and are the same or different with this,
  or the hydrocarbon radical is optionally substituted by a group of the formula -C0 ₂ -R ²⁶ , - CONR27 R28, - _NR 29 _R 30, - NR ³¹ -CO ₂ R ³² or - NR ^33- S0 ₂ R ³⁴ , in which
• _R ^{26 is} alkyl with 1-4 carbon atoms or phenyl, and
• _R 27, _R 28, _R 29, _R 30, _R 3 ¹ , _R 3 ² , _R 33 and R ^{34 have} the meaning given above of R ¹¹ and R ¹² and are the same or different with them, or
• R ^{5 represents} a 5- to 6-membered, saturated or unsaturated heterocycle with up to 2 heteroatoms from the series S, N or O, which is optionally substituted by fluorine, chlorine, methyl, methoxy, methylthio or trifluoromethyl, or
• R ^{5 represents} a group of the formula DR ³⁵ , in which
• D represents the -S (O) _h group or an oxygen atom, wherein
• h represents a number 0, 1 or 2, and
• R ³⁵ denotes phenyl, which is optionally substituted by fluorine, chlorine, bromine, methyl, methoxy, methylthio, trifluoromethyl, amino or by C ₁ -C ₂ -mono- or - dialkylamino, or
• _R ^{35 is} hydrogen, a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical having up to 6 carbon atoms, which is optionally interrupted by oxygen or sulfur and which is optionally substituted by fluorine, chlorine or phenyl, or
  is substituted by a group of the formula - NR36R37 wherein
• R ³⁶ and R ^{37 have} the meaning of R ¹¹ and R ¹² given above and are the same or different with this,

and their salts,
with the proviso that R ^{5 may} not represent optionally halogen-substituted pyridyl or thienyl.

• R¹ für Wasserstoff, Methyl, Ethyl, Trifluormethyl oder Amino steht,
• R⁴ für Wasserstoff, Methyl oder Amino steht,
• R² für eine Gruppe der Formel -CO-NR¹¹R¹² oder -CO-A-R¹³ steht, worin
• R¹¹ und R¹² gleich oder verschieden sind und Wasserstoff oder einen geradkettigen, verzweigten oder cyclischen, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 6 Kohlenstoffatomen bedeuten,
• A eine direkte Bindung oder ein Sauerstoffatom bedeutet,
• R¹³ Wasserstoff oder einen cyclischen, geradkettigen oder verzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 8 Kohlenstoffatomen bedeutet, der gegebenenfalls durch Sauerstoff oder Schwefel oder durch -O-CO-, -CO-O- oder NR¹⁶ unterbrochen ist, worin
• R¹⁶ Wasserstofff oder Methyl bedeutet
  • und der Kohlenwasserstoffrest gegebenenfalls durch Cyclopropyl, Cyclobutyl, Cyclopentyl, Cyclohexyl, Fluor, Chlor, Nitro, Cyano, Hydroxy, -0-N0₂ oder durch Phenyl, Phenoxy, Phenylthio oder Pyridyl substituiert ist, die ihrerseits durch Fluor, Chlor, Methyl, Methoxy, Methylthio, Trifluormethyl oder Trifluormethoxy substituiert sein kann, oder
  • der Kohlenwasserstoffrest gegebenenfalls durch eine Gruppe der Formel -CO₂-R¹⁷, -NH-S0₂-X und/oder -NR²⁰R²¹ substituiert ist, worin
• R¹⁷ Wasserstoff, Methyl oder Ethyl bedeutet,
• R²⁰ und R²¹ gleich oder verschieden sind und Wasserstoff oder einen geradkettigen, verzweigten oder cyclischen, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 5 Kohlenstoffatomen bedeuten, der gegebenenfalls durch Phenyl substituiert ist, das seinerseits durch Fluor, Chlor, Methyl oder Methoxy substituiert sein kann, oder
• R²⁰ und R²¹ gemeinsam unter Einbezug des Stickstoffatoms einen Piperidin- oder Piperazinring bilden, der gegebenenfalls durch Methyl, Ethyl, Phenyl oder Benzyl substituiert sein kann,
• X Phenyl bedeutet, das gegebenenfalls durch Methyl substituiert ist,
• _R ³ für Cyano oder Nitro steht,

oder

• R³ und R⁴ gemeinsam einen Rest der Formel
  
  
  bilden,
  worin
• E ein Sauerstoff- oder Schwefelatom oder die -CH₂-Gruppe bedeutet,
• R⁵ für einen cyclischen, geradkettigen oder verzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 6 Kohlenstoffatomen steht, der gegebenenfalls durch Sauerstoff oder Schwefel unterbrochen ist,
  und der gegebenenfalls durch Cyclopropyl, Cyclobutyl, Cyclopentyl, Cyclohexyl, Fluor, Chlor, Cyano, Hydroxy oder durch Phenyl, Phenyloxy, Phenylthio oder durch einen 5- bis 7-gliedrigen, gesättigten oder ungesättigen Heterocyclus mit bis zu 2 Heteroatomen aus der Reihe S, N oder O substituiert ist, wobei die Cyclen ihrerseits durch Fluor, Chlor, Methyl, Methoxy, Trifluormethyl oder Trifluormethoxy oder durch eine Gruppe der Formel -NR²⁴R²⁵ substituiert sein können, worin
• R²⁴ und R²⁵ Wasserstoff, Phenyl, Benzyl oder geradkettiges oder verzweigtes Alkyl mit bis zu 4 Kohlenstoffatomen bedeuten,
  oder der Kohlenwasserstoffrest gegebenenfalls durch eine Gruppe der Formel -NR29R30 substituiert ist, worin
• R²⁹ und R³⁰ gleich oder verschieden sind und Wasserstoff, Phenyl oder geradkettiges oder verzweigtes Alkyl mit bis zu 4 Kohlenstoffatomen bedeuten, das gegebenenfalls durch Phenyl substituiert ist, oder
• R⁵ für einen 5- bis 6-gliedrigen, gesättigten oder ungesättigten Heterocyclus mit bis zu 2 Heteroatomen aus der Reihe S, N oder O steht, der gegebenenfalls durch Fluor, Chlor, Methyl, Methoxy, Methylthio oder Trifluormethyl substituiert ist, oder
• R⁵ für eine Gruppe der Formel D-R³⁵ steht, worin
• D ein Sauerstoff- oder Schwefelatom bedeutet, und
• R³⁵ Phenyl bedeutet, das gegebenenfalls durch Fluor, Chlor, Methyl, Methoxy, Methylthio, Trifluormethyl, Amino oder durch C1-C2-Mono- oder -Dialkylamino substituiert ist, oder R³⁵ Wasserstoff, einen cyclischen, geradkettigen oder verzweigten, gesättigten oder ungesättigten Kohlenwasserstoffrest mit bis zu 6 Kohlenstoffatomen bedeutet, der gegebenenfalls durch Fluor, Chlor oder Phenyl substituiert ist,
  und deren Salze,
  mit der Maßgabe, daß R⁵ nicht für gegebenenfalls halogensubstituiertes Pyridyl oder Thienyl stehen darf.

Compounds of the general formula (I) in which

• R ^{1 represents} hydrogen, methyl, ethyl, trifluoromethyl or amino,
• R ^{4 represents} hydrogen, methyl or amino,
• R ^{2 represents} a group of the formula -CO-NR ¹¹ R ¹² or -CO-AR ¹³ , wherein
• R ¹¹ and R ^{12 are the} same or different and are hydrogen or a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical with up to 6 carbon atoms,
• A represents a direct bond or an oxygen atom,
• R ^{13 is} hydrogen or a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms, which is optionally interrupted by oxygen or sulfur or by -O-CO-, -CO-O- or NR ¹⁶ , wherein
• R ^{16 means} hydrogen or methyl
  • and the hydrocarbon radical is optionally substituted by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, fluorine, chlorine, nitro, cyano, hydroxy, -0-N0 ₂ or by phenyl, phenoxy, phenylthio or pyridyl, which in turn is substituted by fluorine, chlorine, methyl, methoxy , Methylthio, trifluoromethyl or trifluoromethoxy may be substituted, or
  • the hydrocarbon radical is optionally substituted by a group of the formula -CO ₂ -R ¹⁷ , -NH-S0 ₂ -X and / or -NR ²⁰ R ²¹ , wherein
• R ¹⁷ denotes hydrogen, methyl or ethyl,
• R ²⁰ and R ^{21 are the} same or different and are hydrogen or a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical having up to 5 carbon atoms, which is optionally substituted by phenyl, which in turn can be substituted by fluorine, chlorine, methyl or methoxy , or
• R ²⁰ and R ²¹ together form a piperidine or piperazine ring, including the nitrogen atom, which may optionally be substituted by methyl, ethyl, phenyl or benzyl,
• X denotes phenyl which is optionally substituted by methyl,
• _R ^{3 represents} cyano or nitro,

or

• R ³ and R ⁴ together represent a radical of the formula
  
  
  form,
  wherein
• E represents an oxygen or sulfur atom or the -CH ₂ group,
• R ^{5 represents} a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical with up to 6 carbon atoms, which is optionally interrupted by oxygen or sulfur,
  and optionally by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, fluorine, chlorine, cyano, hydroxy or by phenyl, phenyloxy, phenylthio or by a 5- to 7-membered, saturated or unsaturated heterocycle with up to 2 heteroatoms from the series S, N or O is substituted, the cycles in turn being substituted by fluorine, chlorine, methyl, methoxy, trifluoromethyl or trifluoromethoxy or by a group of the formula -NR ²⁴ R ²⁵ , in which
• R ²⁴ and R ^{25 represent} hydrogen, phenyl, benzyl or straight-chain or branched alkyl having up to 4 carbon atoms,
  or the hydrocarbon radical is optionally substituted by a group of the formula -NR29R30, wherein
• R ²⁹ and R ^{30 are the} same or different and are hydrogen, phenyl or straight-chain or branched alkyl having up to 4 carbon atoms, which is optionally substituted by phenyl, or
• R ^{5 represents} a 5- to 6-membered, saturated or unsaturated heterocycle with up to 2 heteroatoms from the series S, N or O, which is optionally substituted by fluorine, chlorine, methyl, methoxy, methylthio or trifluoromethyl, or
• R ^{5 represents} a group of the formula DR ³⁵ , in which
• D represents an oxygen or sulfur atom, and
• R ^{35 is} phenyl which is optionally substituted by fluorine, chlorine, methyl, methoxy, methylthio, trifluoromethyl, amino or by C1-C2-mono- or dialkylamino, or R ^{35 is} hydrogen, a cyclic, straight-chain or branched, saturated or unsaturated Is a hydrocarbon radical with up to 6 carbon atoms, which is optionally substituted by fluorine, chlorine or phenyl,
  and their salts,
  with the proviso that R ^{5 may} not represent optionally halogen-substituted pyridyl or thienyl.

We have also found a process for preparing the compounds of the general formula (I) according to the invention, characterized in that
in the event that R ^{3 is} cyano, nitro or formyl,

in welcher

• R⁵ die oben angegebene Bedeutung hat,
  zunächst mit Acylverbindungen der allgemeinen Formel (III)
  
  
  in welcher
• R³ und R⁴ die oben angegebene Bedeutung haben
• gegebenenfalls unter Isolierung der Ylidenverbindungen der allgemeinen Formel (IV)
  
  
  in welcher
• R³, R⁴ und R⁵ die oben angegebene Bedeutung haben
• umsetzt, anschließend mit Verbindungen der Formel (V)
  
  
  in welcher
• R¹ und R² die oben angegebene Bedeutung haben,
• und einer reaktiven Ammoniumverbindung, z.B. Ammoniumacetat, oder direkt mit Enamino-Verbindungen der allgemeinen Formel (VI)
  
  
  in welcher
• R¹ und R² die oben angegebene Bedeutung haben, in inerten Lösemitteln umsetzt,
  oder
• [B] Verbindungen der allgemeinen Formel (11) zunächst mit Verbindungen der allgemeinen Formel (V), gegebenenfalls unter Isolierung der Ylidenverbindungen der allgemeinen Formel (VII)
  
  
  in welcher
• R¹, R² und R⁵ die oben angegebene Bedeutung haben,
• umsetzt und anschließend entweder mit Verbindungen der allgemeinen Formel (III) in Gegenwart von Ammoniumverbindungen oder direkt mit Verbindungen der allgemeinen Formel (VIII)
  
  
  in welcher
• R³ und R⁴ die oben angegebenene Bedeutung haben,
  umsetzt
  oder
• [C] im Fall, daß R³ und R⁴ zusammen einen Rest der Formel
  
  
  bilden,
  worin
• E' für ein Sauerstoff- oder Schwefelatom steht,
  zunächst nach dem unter [A] und [B] aufgeführten Methoden Verbindungen der allgemeinen Formel (IX)
  
  
  in welcher
• R¹, R² und R⁵ die oben angegebene Bedeutung haben,
• L für C1-C4-Alkyl steht und
• T für C₁-C₄-Acyloxy oder Acylthio steht,
  herstellt und anschließend einen basischen oder sauren Ringschluß nach bekannten Methoden durchführt, oder
• [D] daß man im Fall, daß E für die -CH₂-Gruppe steht, Verbindungen der allgemeinen Formel (II) zunächst mit Acylverbindungen der allgemeinen Formel (X)
  
  
  
  in welcher
• R² die oben angegebene Bedeutung hat
  und
• L die oben angegebene Bedeutung von R¹ hat, wobei im Fall der Hydroxy-und/oder Aminofunktionen, diese gegebenenfalls in geschützter Form vorliegen,
  gegebenenfalls unter Isolierung der Ylidenverbindungen der allgemeinen Formel (XI)
  
  
  in welcher
• R², R⁵ und L die oben angegebene Bedeutung haben
• umsetzt, anschließend mit der Verbindung der Formel (XII)
  
  
  und einer reaktiven Ammoniumverbindung, z.B. Ammoniumacetat, gegebenenfalls unter Isolierung der Zwischenprodukte der allgemeinen Formel (XIII)
  
  
  in welcher
• R², R³ und L die oben angegebene Bedeutung haben,
  in inerten Lösemitteln umsetzt,
  und anschließend in einem letzten Schritt, gegebenenfalls in Anwesenheit eines Hilfsmittels, Wasser abscheidet.

[A] compounds of the general formula (11)

in which

• R ^{5 has} the meaning given above,
  first with acyl compounds of the general formula (III)
  
  
  in which
• R ³ and R ^{4 have} the meaning given above
• optionally isolating the ylidene compounds of the general formula (IV)
  
  
  in which
• R ³ , R ⁴ and R ^{5 have} the meaning given above
• reacted, then with compounds of the formula (V)
  
  
  in which
• R ¹ and R ^{2 have} the meaning given above,
• and a reactive ammonium compound, for example ammonium acetate, or directly with enamino compounds of the general formula (VI)
  
  
  in which
• R ¹ and R ^{2 have} the meaning given above, are reacted in inert solvents,
  or
• [B] Compounds of the general formula (11) first with compounds of the general formula (V), if appropriate with isolation of the ylidene compounds of the general formula (VII)
  
  
  in which
• R ¹ , R ² and R ^{5 have} the meaning given above,
• reacted and then either with compounds of the general formula (III) in the presence of ammonium compounds or directly with compounds of the general formula (VIII)
  
  
  in which
• R ³ and R ^{4 have} the meaning given above,
  implements
  or
• [C] in the case where R ³ and R ⁴ together are a radical of the formula
  
  
  form,
  wherein
• E 'represents an oxygen or sulfur atom,
  initially by the methods listed under [A] and [B], compounds of the general formula (IX)
  
  
  in which
• R ¹ , R ² and R ^{5 have} the meaning given above,
• L represents C1-C4-alkyl and
• T represents C ₁ -C ₄ -acyloxy or acylthio,
  produces and then carries out a basic or acidic ring closure by known methods, or
• [D] that in the case where E represents the —CH ₂ group, compounds of the general formula (II) are first reacted with acyl compounds of the general formula (X)
  
  
  
  in which
• R ^{2 has} the meaning given above
  and
• L has the meaning of R ¹ given above, where in the case of the hydroxy and / or amino functions, these are optionally present in protected form,
  optionally isolating the ylidene compounds of the general formula (XI)
  
  
  in which
• R ² , R ⁵ and L have the meaning given above
• reacted, then with the compound of formula (XII)
  
  
  and a reactive ammonium compound, for example ammonium acetate, optionally with isolation of the intermediates of the general formula (XIII)
  
  
  in which
• R ² , R ³ and L have the meaning given above,
  reacted in inert solvents,
  and then separating water in a last step, if appropriate in the presence of an auxiliary.

Als Lösemittel eignen sich hierbei alle inerten organischen Lösemittel, die sich unter den Reaktionsbedingungen nicht verändern. Hierzu gehören bevorzugt Alkohole wie Methanol, Ethanol, Propanol oder Isopropanol, oder Ether wie Diethylether, Dioxan, Tetrahydrofuran, Glykoldimethylether, oder Diethylenglykoldimethylether, Acetonitril, oder Amide wie Hexamethylphosphorsäuretriamid oder Dimethylformamid, oder Essigsäure oder halogenierte Kohlenwasserstoffe wie Methylenchlorid, Tetrachlorkohlenstoff oder Kohlenwasserstoffe wie Benzol oder Toluol. Ebenso ist es möglich, Gemische der genannten Lösemittel zu verwenden.The processes according to the invention can be illustrated by the following formula scheme:

All inert organic solvents which do not change under the reaction conditions are suitable as solvents. These preferably include alcohols such as methanol, ethanol, propanol or isopropanol, or ethers such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether, or diethylene glycol dimethyl ether, acetonitrile, or amides such as hexamethylphosphoric acid triamide or dimethylformamide, or acetic acid or halogenated hydrocarbons such as methylene chloride or tetrachloride Toluene. It is also possible to use mixtures of the solvents mentioned.

Depending on the particular process variant, [A], [B], [C] and [D], methanol, isopropanol, ethanol and n-propanol, acetonitrile or tetrahydrofuran are preferred.

The reaction temperatures can be varied over a wide range. In general, one works between + 10 ° C and + 150 ° C, preferably between + 20 _° C and + 100 ° C, especially at the boiling point of the respective solvent.

The reaction can be carried out at normal pressure, but also at elevated or reduced pressure (e.g. 0.5 to 3 bar). Generally one works at normal pressure.

Suitable as chiral ester residues are all esters of enantiomerically pure alcohols, such as, for example, 2-butanol, 1-phenylethanol, lactic acid, lactic acid esters, mandelic acid, mandelic acid esters, 2-amino alcohols, sugar derivatives, hydroxyamino acid derivatives and many other enantiomerically pure alcohols.

The diastereomers are generally separated either by fractional crystallization, by column chromatography or by Craig distribution. Which method is the best one has to be decided on a case by case basis, sometimes it is also advisable to use combinations of the individual methods. Separation by crystallization or Craig distribution or a combination of both processes is particularly suitable.

entweder nach Isolierung oder direkt in situ nach Hydrierung von 4-Nitro-3-hydroxyphthalid der Formel (XV)

mit Verbindungen der allgemeinen Formel (XVI)

zu Verbindungen der allgemeinen Formel (XVII) cyclisiert

diese dann mit üblichen Reduktionsmitteln wie beispielsweise Lithiumaluminiumhydrid oder über ein gemischtes Anhydrid mit Natriumborhydrid in die Alkohole der allgemeinen Formel (XVIII)

The compounds of the general formula (11) are new and can preferably be obtained in analogy to known processes by using 4-amino-3-hydroxyphthalide of the formula (XIV)

either after isolation or directly in situ after hydrogenation of 4-nitro-3-hydroxyphthalide of the formula (XV)

with compounds of the general formula (XVI)

cyclized to compounds of general formula (XVII)

These are then converted into the alcohols of the general formula (XVIII) using customary reducing agents, such as, for example, lithium aluminum hydride or a mixed anhydride with sodium borohydride.

• R⁵ jeweils die oben angegebene Bedeutung hat.

transferred and then oxidized either after isolation or directly in situ with oxidizing agents such as manganese dioxide to give compounds of the general formula (II),
in which

• R ⁵ has the meaning given above.

The procedure can be illustrated using the following formula:

The acyl compounds of the general formulas (III) and (X) are known or can be prepared by customary methods.

The compounds of the general formulas (V), (VI), (VIII) and (XII) are known.

The ylidene compounds (IV), (VII) and (XI) are new, but can be prepared by customary methods.

The compounds of the general formula (IX) are new, but can be prepared by known methods, for example by reacting benzylidene compounds of the general formula (IV) with chloroacetoacetic acid esters and ammonium compounds.

The compounds of the general formula (XIII) are new and can be prepared as described above.

The above manufacturing processes are given for illustration only. The preparation of the compounds of the formula (I) is not restricted to these processes, but any modification of these processes can be used in the same way for the preparation of the compounds according to the invention.

The compounds according to the invention show an unforeseeable, valuable spectrum of pharmacological activity. They influence the contraction power of the heart and the tone of the smooth muscles, in particular they show positive inotropic effects.

They can therefore be used in medicines to influence the pathologically changed blood pressure, as coronary therapeutic agents and for the treatment of heart failure. They can also be used to treat irregular heartbeats, to lower blood sugar, to reduce swelling of the mucous membranes and to influence the salt and fluid balance.

The cardiac and vascular effects were found on the isolated perfused heart of the guinea pig. The hearts of 250 to 350 g guinea pigs are used for this. The animals are killed with one blow to the head, the thorax is opened, and a metal cannula is inserted into the freed-up aorta. The heart is separated from the chest with the lungs and connected to the perfusion apparatus via an aortic cannula while the perfusion is ongoing. The lungs are separated at the roots of the lungs; a Krebs-Henseleit solution (118.5 mmol / I NaCI, 4.75 mmol / I KCI, 1.19 mmol / I KH ₂ P0 ₄ , 1.19 mmol / serves as perfusion medium l MgS0 ₄ , 25 mmol / I NaHC0 ₃ , 0.013 mmol / I Na ₂ EDTA), whose CaCl ₂ content is 1.2 mmol / I. 10 mmol / l glucose are added as the energy-supplying substrate. The solution is filtered particle-free before perfusion. The solution is gassed with carbogen (95% 0 ₂ , 5% CO ₂ ) to maintain the pH 7.4. The hearts are perfused with constant flow (10 ml / min) at 32 ° C using a roller squeeze pump.

To measure cardiac function, a liquid-filled latex balloon, which is connected to a pressure sensor via a liquid column, is inserted through the left atrium into the left ventricle, and the isovolumetric contractions are recorded on a high-speed recorder. The perfusion pressure is registered by means of a pressure sensor, which is connected to the perfusion system in front of the heart. Under these conditions, a decrease in perfusion pressure indicates coronary dilation, an increase or decrease in the left ventricular contraction amplitude a decrease or an increase in cardiac contractility. The compounds according to the invention are perfused in suitable dilutions into the perfusion system shortly before the isolated heart.

The new active compounds can be converted in a known manner into the customary formulations, such as tablets, dragées, pills, granules, aerosols, syrups, emulsions, suspensions and solutions, using inert, non-toxic, pharmaceutically suitable excipients or solvents. The therapeutically active compound should in each case be present in a concentration of about 0.5 to 90% by weight of the total mixture, i.e. in amounts sufficient to achieve the dosage range indicated.

The formulations are prepared, for example, by stretching the active ingredients with solvents and / or carriers, optionally using emulsifiers and / or dispersants, e.g. in the case of the use of water as a diluent, organic solvents can optionally be used as auxiliary solvents.

The application is carried out in the usual way, preferably orally or parenterally, in particular perlingually or intravenously.

In general, it has proven to be advantageous to administer amounts of approximately 0.001 to 1 mg / kg, preferably approximately 0.01 to 0.5 mg / kg of body weight in the case of intravenous administration in order to achieve effective results, and the dosage is approximately in the case of oral administration 0.01 to 20 mg / kg, preferably 0.1 to 10 mg / kg body weight.

Nevertheless, it may be necessary to deviate from the amounts mentioned, depending on the body weight or the type of route of administration, on the individual behavior towards the medicament, the type of its formulation and the time or interval at which the administration takes place . In some cases it may be sufficient to make do with less than the aforementioned minimum quantity, while in other cases the upper limit mentioned must be exceeded. In the case of application of larger quantities, it may be advisable to distribute them in several individual doses over the day.

Output connections example 1 4-Acetoxy-2- (3-phenoxy-quinolin-5-ylidene) -3-oxo-butyric acid ethyl ester

2.49 g (10 mmol) of 3-phenoxyquinoline-5-aldehyde are refluxed in 30 ml of dichloromethane with 2.07 g (11 mmol) of 4-acetoxyacetoacetate, 0.05 ml of acetic acid and 0.1 ml of piperidine in a water separator overnight heated. It is cooled, washed twice with water and concentrated, 4.2 g of a yellowish oil are obtained.

Example 11 Phenylthioacetaldehyde

23 g (1 mol) sodium are dissolved in 400 ml ethanol. After cooling, 110 g (1 mol) of thiophenol are added. 197 g (1 mol) of bromoacetaldehyde diethylacetal are added dropwise to this mixture. It is heated to reflux for 24 hours, cooled and suctioned off from the precipitated salt. It is concentrated, the evaporation residue is mixed with water and extracted 3 times with ether. The combined ether phases are washed with 1 N sodium hydroxide solution and water, dried and concentrated. The evaporation residue obtained is dissolved in 1.2 l of THF, mixed with 1 l of dilute hydrochloric acid and heated to reflux for 3 hours. It is cooled, diluted with water, extracted 3 times with ether, the combined ether phases are washed with water, sodium hydrogen carbonate solution and again water, dried and concentrated. 150 g of crude oil are obtained, which is reacted without further purification.

Example 111 3-phenylthio-quinoline-5-carboxylic acid

100 g (0.512 mol) of 3-hydroxy-4-nitro-phthalide are hydrogenated in 500 ml of ethanol after addition of 10 g of Pd / barium sulfate at 3.5 bar, the temperature being allowed to rise to 50 ° C. It is suctioned off warm. 75 g (0.5 mol) of the compound from Example II are added to the filtrate and the mixture is heated under reflux overnight. The precipitated product is filtered off after cooling and washed with ethanol. 35 g of an almost colorless compound of melting point 287-289 ° C. are obtained.

Example IV 5-hydroxymethyl-3-phenylthioquinoline

28.1 g (0.1 mol) of the compound from Example III are dissolved in 800 ml of dry THF and 200 ml of a 1 molar solution of lithium aluminum hydride in THF are added dropwise at 20-30 ° C. The mixture is stirred at room temperature for 3 hours. 8 ml of water and 24 ml of dilute potassium hydroxide solution are added dropwise in succession with ice cooling. The mixture is stirred for 1 hour, suction filtered through Celite and washed with THF. After concentrating the filtrate, 27 g of crude product are obtained, which is reacted further without purification.

Example V 3-phenylthio-quinoline-5-aldehyde

27 g of the compound from Example IV are dissolved in a mixture of 500 ml of dimethoxyethane and 500 ml of dichloromethane, and 165 g of manganese dioxide are added. The mixture is stirred at room temperature for 2 hours, suction filtered over Celite and washed with dichloromethane. After concentration, the evaporation residue obtained is purified by flash chromatography with toluene / ethyl acetate mixtures. 13.7 g of almost colorless crystals with a melting point of 46-47 ° C. are obtained.

Example VI 3-cyclohexyl-quinoline-5-carboxylic acid

A mixture of 50 g of 4-nitro-3-hydroxyphthalide in 200 ml of isopropanol is hydrogenated with 5 g of Pd / barium sulfate at 3.5 bar, the temperature rising to 55 _° C. After the hydrogenation has ended (about 30 minutes), the catalyst is suctioned off while warm. 33 g (260 mmol) of cyclohexylacetaldehyde are added to the filtrate and, after the addition of a catalytic amount of sodium methylate, the mixture is heated under reflux for 20 hours. The precipitated crystals are filtered off after cooling and washed with isopropanol. 15 g of almost colorless product with a melting point above 280 ° C. are obtained.

Example VII 3-cyclohexyl-5-hydroxymethyl-quinoline

33.6 g (131.7 mmol) of the compound from Example VI are dissolved in 320 ml of dimethoxyethane and stirred with 197.6 mmol (27.6 ml) of triethylamine. After 30 minutes, 19.75 ml (197.5 mmol) of ethyl chlorocarbonate are added dropwise at 20-30 _° C.

The mixture is stirred for 30 minutes, suctioned off from the salt and washed with dimethoxyethane. The filtrate is concentrated and dissolved in a mixture of 320 ml of ethanol and 160 ml of water and a solution of 9.25 g of sodium borohydride in 54 ml of water is added dropwise at 15-18 _° C. The mixture is stirred at room temperature for 1 hour, filtered off with salt and washed with ethanol and water. The filtrate is concentrated up to a third, dichloromethane and water are added and the mixture is separated. The organic phase is washed 3 times with water, dried and concentrated. 26 g of a light brown oil are obtained, which is used without further purification.

Example VIII 3-cyclohexyl-quinoline-5-aldehyde

26 g of compound VII in 260 ml of dichloromethane are mixed with 150 g of manganese dioxide. The mixture is stirred for 1 hour, suction filtered and washed with dichloromethane. The filtrate is concentrated. Min receives 20 g of a crystalline compound which melts after recrystallization from acetonitrile at 94-95 ° C.

Manufacturing examples example 1

3-Cyano-1,4-dihydro-2,6-dimethyl-4- (3-benzyl-quinolin-5-yl) pyridine-5-carboxylic acid isopropyl ester

1.24 g (5 mmol) of 3-benzylquinoline-5-aldehyde in 20 ml of dichloromethane are mixed with 0.72 g of isopropyl acetoacetate, 0.025 ml of acetic acid and 0.05 ml of piperidine and heated to boiling overnight. It is cooled, diluted with dichloromethane, shaken twice with water, dried and concentrated, the intermediate obtained is suspended in 15 ml of isopropanol, mixed with 0.41 g (5 mmol) of 3-aminocrotononitrile and stirred at 80 ° C. for 20 hours concentrated and purified by flash chromatography with toluene / ethyl acetate mixtures. After crystallization from ethanol / ether 1: 1, 1.0 g of colorless crystals of melting point 188-190 ° C.

Example 2 2-Methyl-4- (3-phenoxy-quinolin-5-yl) -5-oxo-1,4,5,7-tetrahydrofuro [3,4-b] pyridine-3-carboxylic acid ethyl ester

a) Preparation of the starting compound Diethyl 2-acetoxy-6-methyl-4- (3-phenoxy-quinolin-5-yl) -1,4-dihydropyridine-3,5-dicarboxylic acid

4.2 g (10 mmol) of the compound from Example are refluxed in 50 ml of isopropanol with 1.4 g (11 mmol) of 3-aminocrotonic acid ethyl ester for 20 hours and concentrated. 5.4 g of a brown oil are obtained.

5.4 g of the compound from Example 2a are dissolved in 60 ml of ethanol, 1.5 g of powdered potassium hydroxide are added and the mixture is heated under reflux for 1 hour. It is cooled, neutralized with 1N hydrochloric acid and concentrated. The evaporation residue is taken up in dichloromethane, washed with water, dried and concentrated. After crystallization with ethyl acetate, the product is filtered off with suction and washed with ethyl acetate. 1.1 g of a colorless compound with a melting point of 218-219 ° C. are obtained.

• In Analogie zur Vorschrift des Beispiels 2 werden die in den Tabellen 2 und 4 aufgeführten Verbindungen hergestellt:
  
  
  
  
  
  
  
  
  
  

The compounds listed in Tables 1, 3, 5, 6 and 7 are prepared in analogy to the instructions in Example 1:

• The compounds listed in Tables 2 and 4 are prepared analogously to the instructions in Example 2:
  
  
  
  
  
  
  
  
  
  

Claims (11)

1. 3-quinolyl substituted dihydropyridines of the general formula (I)
in which R ¹ and R ^{4 are} identical or different and represent hydrogen, amino, cyano, formyl, trifluoromethyl or straight-chain or branched alkyl having up to 8 carbon atoms, which may be substituted by hydroxyl or by a group of the formula - NR6 R7, -O- CO-R ⁸ , -O- (CH ₂ ) _a -OR ^{8 '} or -O- (CH ₂ ) _b -NR ⁹ R ^{10 is} substituted, wherein R ⁶ , R ⁷ , R ⁹ and R ^{10 are} identical or different and denote hydrogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms, R ⁸ and R ⁸ 'are identical or different and denote straight-chain or branched alkyl having up to 6 carbon atoms, and a and b are the same or different and represent a number 2, 3, 4 or 5, R ^{2 represents} a group of the formula - CO-NR ¹¹ R ¹² or -CO-AR ¹³ , wherein R ¹¹ and R ^{12 are the} same or different and are hydrogen, a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical with up to 8 carbon atoms, which may be halogen, hydroxy, cyano or aryl, aryloxy, arylthio with 6 to 10 each Carbon atoms or by a 5- to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O is substituted, the cycles in turn by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, Alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each with up to 4 carbon atoms can be substituted, or
Aryl with 6 to 10 carbon atoms or a 5 to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O, which are optionally up to 2 times the same or different by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 4 carbon atoms, or R ¹¹ and R ¹² together, including the nitrogen atom, form a 3 to 8-membered, saturated or unsaturated heterocycle which may be interrupted by an oxygen atom or by a radical of the formula S (O) _d , - CO- or -NR ¹⁵ can in what d represents a number 0, 1 or 2, R ^{15 is} hydrogen or aryl having 6 to 10 carbon atoms, optionally up to 2 times the same or different by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl each having up to 8 carbon atoms, haloalkyl, haloalkoxy or haloalkylthio is each substituted with up to 4 carbon atoms, or is a cyclic, saturated or unsaturated, straight-chain or branched hydrocarbon radical having up to 8 carbon atoms, which may be by hydroxyl, halogen or aryl having 6 to 10 carbon atoms or a 5 to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms from the series S, N or O is substituted, the cycles themselves being up to 2 times identical or different by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio, each with up to 4 Carbon atoms can be substituted, and the heterocycle optionally by straight-chain or branched alkoxy or alkylthio each having up to 4 carbon atoms, halogen, aryl having 6 to 10 carbon atoms, a 5 to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms the series S, N or O or by straight-chain o the branched alkyl is substituted with up to 4 carbon atoms, which in turn can be substituted with aryl with 6 to 10 carbon atoms, A represents a direct bond or an oxygen atom, R ^{13 is} hydrogen or aryl having 6 to 10 carbon atoms or a 5- to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O, the cycles optionally up to 3 times the same or different are substituted by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 4 carbon atoms, or
is a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical having up to 10 carbon atoms, which may be up to 3 times the same or different by oxygen or by - CO-, -CO-NH-, -O-CO-, -CO -O-, -NH-CO-, -S0 ₂ -NH-, -NH-S0 ₂ -, -S- (O) _e -or-NR ¹⁶ - is interrupted, wherein e has the meaning of d given above and is the same or different with it, R ^{16 has} the meaning of R ¹⁵ given above and is the same or different with it,
or the hydrocarbon radical optionally up to 3 times the same or different by arylidene having 6 to 10 carbon atoms or heterocyclic radicals of the formulas

is interrupted
wherein f and g are the same or different and represent a number 1 or 2, and arylidene can be substituted by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio, each having up to 4 carbon atoms,
and the hydrocarbon radical optionally up to 3 times the same or different by cycloalkyl having 3 to 8 carbon atoms, halogen, nitro, cyano, hydroxy, - O-N0 ₂ , straight-chain or branched alkylthio, alkoxy or acyloxy each having up to 8 carbon atoms or by Aryl, aryloxy or arylthio each having 6 to 10 carbon atoms or by a 5- to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O is substituted, where the cycles themselves may be substituted up to three times, identically or differently, by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio, each having up to 4 carbon atoms, or
the hydrocarbon radical is optionally substituted by a group of the formula -C02-R17, -CONR ¹⁸ R ¹⁹ , - NR ²⁰ R ²¹ , -NH-S0 ₂ -X and / or -NR ²² -CO ₂ R ²³ , wherein R ^{17 has} the meaning of R ¹⁵ given above and is the same or different with it and R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² and R ^{23 have} the abovementioned meaning of R ¹¹ and R ¹² and are the same or different with these, and X denotes phenyl which is optionally substituted by methyl, _R 3 represents cyano, nitro or formyl,
or R ³ and R ⁴ together represent a radical of the formula

form,
wherein E represents an oxygen or sulfur atom or the --CH ₂ group, R ^{5 represents} a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical with up to 12 carbon atoms, which is optionally interrupted up to 2 times by the same or different means by oxygen or sulfur,
and optionally up to 3 times the same or different by cycloalkyl having 3 to 8 carbon atoms, straight-chain or branched acyloxy having up to 4 carbon atoms, halogen, nitro, cyano, hydroxy or by aryl, aryloxy or arylthio each having 6 to 10 carbon atoms or is substituted by a 5- to 7-membered, saturated or unsaturated optionally fused heterocycle with up to 5 heteroatoms from the series S, N or O, the cycles themselves being up to 3 times identical or different by halogen, cyano, nitro, Hydroxy or by straight-chain or branched alkyl or alkoxy each having up to 4 carbon atoms, trifluoromethyl, trifluoromethoxy, trifluoromethylthio or by a group of the formula - NR ²⁴ R ²⁵ , where R ²⁴ and R ^{25 have} the meaning of R ¹¹ and R ¹² given above and are identical or different with these,
or the hydrocarbon radical is ^optionally substituted by a group of the formula - C0 ₂ -R ²⁶ , - CONR27 R28, - NR ²⁹ R ³⁰ , - NR ³¹ -CO ₂ R ³² or -NR ^33- S0 ₂ R ³⁴ , wherein R ^{26 has} the meaning of R ¹⁵ given above and is the same or different with it and _R 27, _R 28, _R 29, _R 30, _R 3 ¹ , _R 3 ² , _R 33 and R ^{34 have} the meaning given above of R ¹¹ and R ¹² and are the same or different with them, or R ^{5 represents} a 5- to 7-membered, saturated or unsaturated heterocycle with up to 4 heteroatoms from the series S, N or O, which may be up to 3 times the same or different by halogen, amino, cyano, nitro or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 4 carbon atoms or substituted by C1-C4-mono- or dialkylamino, or R ^{5 represents} a group of the formula DR ³⁵ , in which D represents the CO or S (O) _h group or an oxygen atom, in which h represents a number 0, 1 or 2, and _R 3 ⁵ is aryl having 6 to 10 carbon atoms or a 5-to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms from the series S, N or O, which are optionally substituted up to 3 times in an identical or different manner by halogen, Amino, cyano, nitro or substituted by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio, each having up to 4 carbon atoms, or by C ₁ -C ₄ mono- or dialkylamino, or _R 3 ^{5 is} hydrogen or a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical with up to 8 carbon atoms, which is optionally interrupted by oxygen or sulfur,
and which is optionally substituted by halogen, aryl, aryloxy or arylthio each having 6 to 10 carbon atoms or by a 5 to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms from the series S, N or O, the cycles being in turn can be substituted by halogen, trifluoromethyl, methyl, methoxy, nitro or methylthio, or
is substituted by a group of the formula - NR36R37, wherein R ³⁶ and R ^{37 have} the meaning of R ¹¹ and R ¹² given above and are the same or different with these,
and their salts,
with the proviso that R ^{5 may} not represent optionally halogen-substituted pyridyl or thienyl. 2. Compounds of general formula (I) according to claim 1, in which R ¹ and R ^{4 are the} same or different and represent hydrogen, amino, cyano, Formyl, trifluoromethyl or straight-chain or branched alkyl having up to 4 carbon atoms, optionally by hydroxy, by a group of the formula - NR ⁶ R ⁷ , -O-CO-R ⁸ , -O- (CH ₂ ) _a -OR ^{8 '} or -O- (CH ₂ ) _b , -NR ⁹ R' °, wherein R ⁶ , R ⁷ , R ⁹ and R ^{10 are} identical or different and denote hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, R ⁸ and R ⁸ 'are identical or different and represent straight-chain or branched alkyl having up to 4 carbon atoms, and a and b are the same or different and represent a number 2, 3, 4 or 5, R ^{2 represents} a group of the formula - CO-NR ¹¹ R ¹² or -CO-AR ¹³ , wherein R ¹¹ and R ^{12 are the} same or different and are hydrogen, a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical having up to 6 carbon atoms, which is optionally substituted by fluorine, chlorine, hydroxy, phenyl or pyridyl, the cycles in turn by Fluorine, chlorine or substituted by alkyl, alkoxy, alkylthio or alkoxycarbonyl each having up to 2 carbon atoms, trifluoromethyl or trifluoromethoxy, or
Phenyl or pyridyl, which are optionally substituted by fluorine, chlorine or by alkyl, alkoxy, alkylthio or alkoxycarbonyl each having up to 2 carbon atoms, trifluoromethyl or trifluoromethoxy, or R ¹¹ and R ¹² together and inclusion of the nitrogen atom form a 3 to 8-membered, saturated or unsaturated heterocycle which may be interrupted by an oxygen atom or by a radical of the formula S (O) _d , - CO- or -NR ¹⁵ can in what d represents a number 0, 1 or 2, R ¹⁵ denotes hydrogen or phenyl, which is optionally substituted by fluorine, chlorine, methyl, ethyl, methoxy, ethoxy, trifluoromethyl or trifluoromethoxy, or
is a cyclic, saturated or unsaturated, straight-chain or branched hydrocarbon radical having up to 4 carbon atoms, which may be by fluorine, chlorine, phenyl or by a 5- to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms from the S series, N or O is substituted, where the cycles can themselves be substituted by fluorine, chlorine, methyl, methoxy, methylthio, trifluoromethyl or trifluoromethoxy, A represents a direct bond or an oxygen atom, R ¹³ denotes hydrogen, phenyl or pyridyl, which are optionally substituted by fluorine, chlorine, methyl, methoxy, methylthio, trifluoromethyl or trifluoromethoxy, or
is a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms, which may be up to 2 times the same or different by oxygen or by - CO-, -CO-NH-, -O-CO-, -CO -O-, -NH-CO-, -S0 ₂ -NH-, -NH-S0 ₂ -, -S (O) _e -or-NR ¹⁶ - is interrupted, wherein e has the meaning of d given above and is the same or different with it, R ^{16 has} the meaning of R ¹⁵ given above and with this is the same or different,
or the hydrocarbon radical optionally up to 2 times the same or different by arylidene having 6 to 10 carbon atoms or heterocyclic radicals of the formulas

is interrupted
wherein f and g are the same or different and represent a number 1 or 2,
and the hydrocarbon radical optionally up to 2 times the same or different by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, fluorine, chlorine, nitro, cyano, hydroxy, -0-N0 ₂ , straight-chain or branched alkylthio, alkoxy or acyloxy, each with up to 4 Carbon atoms or substituted by phenyl, phenoxy, phenylthio or pyridyl, where the cycles in turn can be substituted by fluorine, chlorine, cyano, methyl, methoxy, methylthio, trifluoromethyl or trifluoromethoxy, or the hydrocarbon radical optionally by a group of the formula -C02-R17 , -CONR ¹⁸ R ¹⁹ , - NR ²⁰ R ²¹ , -NH-S0 ₂ -X and / or -NR ²² -CO ₂ R ^{23 is} substituted, wherein R ^{17 has} the meaning of R ¹⁵ given above and is the same or different with it and R ¹⁸ , R ' ⁹ , R ²⁰ , R ²¹ , R ²² and R ^{23 have} the abovementioned meaning of R ¹¹ and R ¹² and are the same or different with these, and X denotes phenyl which is optionally substituted by methyl, _R ^{3 represents} cyano, nitro or formyl,
or R ³ and R ⁴ together represent a radical of the formula

form,
wherein E represents an oxygen or sulfur atom or the --CH ₂ group, R ^{5 represents} a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical with up to 10 carbon atoms, which is optionally interrupted by oxygen or sulfur, and which is optionally up to 2 times identical or different by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Fluorine, chlorine, bromine, acyloxy with up to 2 carbon atoms, cyano, hydroxy or through phenyl, phenyloxy, phenylthio or through a 5- to 7-membered, saturated or unsaturated heterocycle with bis is substituted to 3 heteroatoms from the series S, N or O, the phenyl and the heterocycles in turn being up to 2 times identical or different by fluorine, chlorine, bromine, hydroxyl, methyl, ethyl, methoxy, ethoxy, trifluoromethyl , Trifluoromethoxy or trifluoromethylthio or can be substituted by a group of the formula - NR ²⁴ R ²⁵ , wherein R ²⁴ and R ^{25 have} the abovementioned meaning of R ¹¹ and R ¹² and are the same or different with them, or the hydrocarbon radical optionally by a group of the formula - C0 ₂ -R ²⁶ , - CONR27 R28, - NR ²⁹ R ³⁰ , - NR ³¹ -CO ₂ R ³² or -NR ^33- S0 ₂ R ^{34 is} substituted, wherein R ^{26 has} the meaning of R ¹⁵ given above and is the same or different with it and _R 27, _R 28, _R 29, _R 3 ⁰ , _R 3 ¹ , R ³² , R ³³ and R ^{34 have} the meaning given above of R ¹¹ and R ¹² and are the same or different with these, or R ^{5 represents} a 5- to 7-membered, saturated or unsaturated heterocycle with up to 4 heteroatoms from the series S, N or O, which may be up to 2 times identical or different due to fluorine, chlorine, bromine, cyano, nitro or is substituted by alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 2 carbon atoms, amino or by C ₁ -C ₄ mono- or dialkylamino, or R ^{5 represents} a group of the formula DR ³⁵ , in which D represents the CO or S (O) _h group or an oxygen atom, in which h represents a number 0, 1 or 2, and _R 3 ^{5 is} phenyl or a 5 to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O, which may be up to 2 times the same or different by fluorine, chlorine, bromine, cyano , Nitro or are substituted by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 4 carbon atoms, amino or by C ₁ -C ₄ mono-or - dialkylamino, or _R 3 ^{5 is} hydrogen or a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms, which is optionally interrupted by oxygen or sulfur and which may be substituted by fluorine, chlorine, phenyl, phenoxy or phenylthio, or
is substituted by a group of the formula - NR36R37, wherein R ³⁶ and R ^{37 have} the meaning of R ¹¹ and R ¹² given above and are the same or different with it, and their salts, with the proviso that R ^{5 may} not represent optionally halogen-substituted pyridyl or thienyl. 3. Compounds of general formula (I) according to claim 1, in which R ¹ and R ^{4 are the} same or different and represent hydrogen, amino, trifluoromethyl, methyl or ethyl, R ^{2 represents} a group of the formula - CO-NR ¹¹ R ¹² or -CO-AR ¹³ , wherein R ¹¹ and R ^{12 are the} same or different and are hydrogen, a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical having up to 6 carbon atoms, or are phenyl which is optionally substituted by fluorine, chlorine, methyl or methoxy, A represents a direct bond or an oxygen atom, R ^{13 is} hydrogen or a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms, which may be by oxygen or sulfur or by - CO-NH-, -O-CO-, -CO-O-, -NH -CO-, -S0 ₂ -NH-, -NH-S0 ₂ - or -NR ' ⁶ -interrupted, wherein R ^{16 is} hydrogen, straight-chain or branched alkyl having up to 4 carbon atoms, or the hydrocarbon radical by heterocyclic radicals of the formulas

is interrupted in what f and g are the same or different and represent a number 1 or 2, and the hydrocarbon radical is optionally substituted by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, fluorine, chlorine, nitro, cyano, hydroxy or by phenyl, phenoxy, phenylthio or pyridyl, which in turn can be substituted by fluorine, chlorine, methyl, methoxy, methylthio, trifluoromethyl or trifluoromethoxy, or the hydrocarbon radical optionally by a group of the formula -C0 ₂ R ¹⁷ , -CONR ¹⁸ R ¹⁹ , - NR ²⁰ R ²¹ , -NH-S0 ₂ -X and / or -NR ^22- C0 ₂ R ^{23 is} substituted, wherein R ²⁰ and R ^{21 are} identical or different and are hydrogen, a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical having up to 6 carbon atoms, which is optionally substituted by fluorine, chlorine, pyridyl or phenyl, which in turn is substituted by fluorine, chlorine, Methyl or methoxy may be substituted, or
Phenyl, which is optionally substituted by fluorine, chlorine, methyl or methoxy, or R ²⁰ and R ²¹ together, including the nitrogen atom, form a 5-to 6-membered, saturated or unsaturated heterocycle which may optionally contain up to 2 further heteroatoms from the S, N or O series and which may also be straight-chain or ver branched alkyl is substituted with up to 4 carbon atoms, benzyl or phenyl, X denotes phenyl, which is optionally substituted by methyl. R ¹⁷ , R ¹⁸ , R ' ⁹ , R ²² and R ^{23 are} identical or different and denote hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, which is optionally substituted by phenyl, or phenyl, which is optionally substituted by fluorine, chlorine or bromine is substituted, _R ^{3 represents} cyano, nitro or formyl,
or R ³ and R ⁴ together represent a radical of the formula

form,
wherein E represents an oxygen or sulfur atom or the --CH ₂ group, R ^{5 represents} a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms, which is optionally interrupted by oxygen or sulfur, and which is optionally interrupted by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, fluorine, chlorine, nitro, cyano, Hydroxy or by phenyl, phenoxy, phenylthio or by a 5- to 7-membered, saturated or unsaturated heterocycle with up to 2 heteroatoms from the series S, N or O is substituted, the phenyl and the heterocycles in turn up to 2 times the same or different can be substituted by fluorine, chlorine, methyl, methoxy, trifluoromethyl or trifluoromethoxy or by a group of the formula - NR ²⁴ R ²⁵ , in which R ²⁴ and R ^{25 have} the meaning of R ¹¹ and R ¹² given above and are the same or different with this,
or the hydrocarbon radical is ^optionally substituted by a group of the formula - C0 ₂ -R ²⁶ , - CONR27 R28, - NR ²⁹ R ³⁰ , - NR ³¹ -CO ₂ R ³² or -NR ^33- S0 ₂ R ³⁴ , wherein _R ^{26 is} alkyl with 1-4 carbon atoms or phenyl, and _R 27, _R 28, _R 29, _R 3 ⁰ , _R 3 ¹ , R ³² , R ³³ and R ^{34 have} the meaning given above of R ¹¹ and R ¹² and are the same or different with these, or R ^{5 represents} a 5- to 6-membered, saturated or unsaturated heterocycle with up to 2 heteroatoms from the series S, N or O, which is optionally substituted by fluorine, chlorine, methyl, methoxy, methylthio or trifluoromethyl, or R ^{5 represents} a group of the formula DR ³⁵ , in which D represents the - S (O) _h group or an oxygen atom, wherein h represents a number 0, 1 or 2, and _R ³⁵ denotes phenyl which is optionally substituted by fluorine, chlorine, bromine, methyl, methoxy, methylthio, trifluoromethyl, amino or by Ci-C2-mono- or dialkylamino, or _R ^{35 is} hydrogen, a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical having up to 6 carbon atoms, which is optionally interrupted by oxygen or sulfur and which is optionally substituted by fluorine, chlorine or phenyl, or by a group of the formula - NR36R37 is substituted in which R ³⁶ and R ^{37 have} the meaning of R ¹¹ and R ¹² given above and are the same or different with this,
and their salts,
with the proviso that R ^{5 may} not represent optionally halogen-substituted pyridyl or thienyl. 4. Compounds of general formula (I) according to claim 1, in which R ^{1 represents} hydrogen, methyl, ethyl, trifluoromethyl or amino, R ^{4 represents} hydrogen, methyl or amino, R ^{2 represents} a group of the formula -CO-NR ¹¹ R ¹² or -CO-AR ¹³ , wherein R ¹¹ and R ^{12 are} identical or different and denote hydrogen or a saturated or unsaturated straight-chain, branched or cyclic hydrocarbon radical having up to 6 carbon atoms, A represents a direct bond or an oxygen atom, R ^{13 is} hydrogen or a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms, which is optionally interrupted by oxygen or sulfur or by -O-CO-, -CO-O- or -NR ' ⁶ , in which R ^{16 represents} hydrogen or methyl,
and the hydrocarbon radical is optionally substituted by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, fluorine, chlorine, nitro, cyano, hydroxy, -0-N0 ₂ or by phenyl, phenoxy, phenylthio or pyridyl, which in turn is substituted by fluorine, chlorine, methyl, methoxy , Methylthio, trifluoromethyl or trifluoromethoxy may be substituted, or
the hydrocarbon radical is optionally substituted by a group of the formula -C02R17, -NH-S0 ₂ X and / or -NR ²⁰ R ²¹ , wherein _R ¹⁷ denotes hydrogen, methyl or ethyl, R ²⁰ and R ^{21 are the} same or different and are hydrogen or a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical having up to 5 carbon atoms, which is optionally substituted by phenyl, which in turn can be substituted by fluorine, chlorine, methyl or methoxy , or R ²⁰ and R ²¹ together form a piperidine or piperazine ring, including the nitrogen atom, which may optionally be substituted by methyl, ethyl, phenyl or benzyl, X denotes phenyl which is optionally substituted by methyl, _R ^{3 represents} cyano or nitro,
or R ³ and R ⁴ together represent a radical of the formula

form,
wherein E represents an oxygen or sulfur atom or the -CH ₂ group, R ^{5 represents} a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical with up to 6 carbon atoms, which is optionally interrupted by oxygen or sulfur,
and optionally by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, fluorine, chlorine, cyano, hydroxy or by phenyl, phenyloxy, phenylthio or by a 5- to 7-membered, saturated or unsaturated heterocycle with up to 2 heteroatoms from the series S, N or O is substituted, the cycles in turn being substituted by fluorine, chlorine, methyl, methoxy, trifluoromethyl or trifluoromethoxy or by a group of the formula - NR ²⁴ R ²⁵ , in which R ²⁴ and R ^{25 represent} hydrogen, phenyl, benzyl or straight-chain or branched alkyl having up to 4 carbon atoms,
or the hydrocarbon radical is optionally substituted by a group of the formula - _NR ²⁹ R ³ °, wherein R ²⁹ and R ^{30 are the} same or different and are hydrogen, phenyl or straight-chain or branched alkyl having up to 4 carbon atoms, which is optionally substituted by phenyl, or R ^{5 represents} a 5- to 6-membered, saturated or unsaturated heterocycle with up to 2 heteroatoms from the series S, N or O, which is optionally substituted by fluorine, chlorine, methyl, methoxy, methylthio or trifluoromethyl, or R ^{5 represents} a group of the formula DR ³⁵ , in which D represents an oxygen or sulfur atom, and R ³⁵ denotes phenyl, which is optionally substituted by fluorine, chlorine, methyl, methoxy, methylthio, trifluoromethyl, amino or by C ₁ -C ₂ -mono- or dialkylamino, or R ³⁵ denotes hydrogen, a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical with up to 6 carbon atoms, which is optionally substituted by fluorine, chlorine or phenyl,
and their salts,
with the proviso that R ^{5 may} not represent optionally halogen-substituted pyridyl or thienyl. 5. Process for the preparation of compounds of the general formula (I)

in which R ¹ and R ^{4 are} identical or different and represent hydrogen, amino, cyano, formyl, trifluoromethyl or straight-chain or branched alkyl having up to 8 carbon atoms, which may be substituted by hydroxyl or by a group of the formula - NR ⁶ R ⁷ , - O-CO-R ⁸ , -O- (CH ₂ ) _a -OR ^{8 '} or -O- (CH ₂ ) _b , -NR ⁹ R ¹⁰ , wherein R ⁶ , R ⁷ , R ⁹ and R ^{10 are} identical or different and denote hydrogen, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms, R ⁸ and R ⁸ 'are identical or different and denote straight-chain or branched alkyl having up to 6 carbon atoms, and a and b are the same or different and represent a number 2, 3, 4 or 5, R ^{2 represents} a group of the formula - CO-NR ¹¹ R ¹² or -CO-AR ¹³ , wherein R ¹¹ and R ^{12 are the} same or different and are hydrogen, a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon radical with up to 8 carbon atoms, which may be halogen, hydroxy, cyano or aryl, aryloxy, arylthio with 6 to 10 each Carbon atoms or by a 5- to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O is substituted, the cycles in turn by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, Alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each with up to 4 carbon atoms can be substituted, or
Aryl with 6 to 10 carbon atoms or a 5 to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O, which are optionally up to 2 times the same or different by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 4 carbon atoms, or R ¹¹ and R ¹² together, including the nitrogen atom, form a 3 to 8-membered, saturated or unsaturated heterocycle which may be interrupted by an oxygen atom or by a radical of the formula S (O) _d , - CO- or -NR ¹⁵ can in what d represents a number 0, 1 or 2, R ^{15 is} hydrogen or aryl having 6 to 10 carbon atoms, optionally up to 2 times the same or different Halogen, cyano or substituted by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl each having up to 8 carbon atoms, haloalkyl, haloalkoxy or haloalkylthio each having up to 4 carbon atoms, or is a cyclic, saturated or unsaturated, straight-chain or branched hydrocarbon radical having up to 8 carbon atoms, which may be by hydroxyl, halogen or aryl having 6 to 10 carbon atoms or a 5 to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms from the series S, N or O is substituted, the cycles themselves being up to 2 times identical or different by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio, each with up to 4 Carbon atoms can be substituted, and the heterocycle optionally by straight-chain or branched alkoxy or alkylthio each having up to 4 carbon atoms, halogen, aryl having 6 to 10 carbon atoms, a 5 to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms from the series S, N or O or is substituted by straight-chain or branched alkyl having up to 4 carbon atoms, which in turn can be substituted by aryl having 6 to 10 carbon atoms, A represents a direct bond or an oxygen atom, _R ^{13 is} hydrogen or aryl having 6 to 10 carbon atoms or a 5- to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O, the cycles optionally being up to 3 times identical or different are substituted by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 4 carbon atoms, or
is a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical having up to 10 carbon atoms, which may be up to 3 times the same or different by oxygen or by - CO-, -CO-NH-, -O-CO-, -CO -O-, -NH-CO-, -S0 ₂ -NH-, -NH-S0 ₂ -, -S (O), - or -NR ' ^{6- is} interrupted, wherein e has the meaning of d given above and is the same or different with it, R ^{16 has} the meaning of R ¹⁵ given above and is the same or different with it,
or the hydrocarbon radical optionally up to 3 times the same or different by arylidene having 6 to 10 carbon atoms or heterocyclic radicals of the formulas

is interrupted in what f and g are the same or different and represent a number 1 or 2, and wherein arylidene is represented by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, Haloalkyl, haloalkoxy or haloalkylthio can each be substituted with up to 4 carbon atoms,
and the hydrocarbon radical optionally up to 3 times the same or different by cycloalkyl having 3 to 8 carbon atoms, halogen, nitro, cyano, hydroxy, - O-N0 ₂ , straight-chain or branched alkylthio, alkoxy or acyloxy each having up to 8 carbon atoms or by Aryl, aryloxy or arylthio each having 6 to 10 carbon atoms or by a 5- to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O is substituted, the cycles in turn up to 3 times may be substituted, identically or differently, by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio, each having up to 4 carbon atoms, or
the hydrocarbon radical is optionally substituted by a group of the formula -C02-R17, -CONR ¹⁸ R ¹⁹ , - NR ²⁰ R ²¹ -NH-S0 ₂ -X and / or -NR ²² -CO ₂ R ²³ , wherein R ^{17 has} the meaning of R ¹⁵ given above and is the same or different with it and R ¹⁸ , R ' ⁹ , R ²⁰ , R ²¹ , R ²² and R ^{23 have} the abovementioned meaning of R ¹¹ and R ¹² and are the same or different with these, X denotes phenyl which is optionally substituted by methyl, _R ^{3 represents} cyano, nitro or formyl,
or R ³ and R ⁴ together represent a radical of the formula

form,
wherein E represents an oxygen or sulfur atom or the --CH ₂ group, R ^{5 represents} a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical with up to 12 carbon atoms, which is optionally interrupted up to 2 times the same or different by oxygen or sulfur, and which is optionally up to 3 times the same or different Cycloalkyl having 3 to 8 carbon atoms, straight-chain or branched acyloxy having up to 4 carbon atoms, halogen, nitro, cyano, hydroxy or by aryl, aryloxy or arylthio each having 6 to 10 carbon atoms or by a 5 to 7-membered, saturated or unsaturated optionally condensed heterocycle is substituted with up to 5 heteroatoms from the series S, N or 0, the cycles themselves being up to 3 times the same or different by halogen, cyano, nitro, hydroxyl or by straight-chain or branched alkyl or alkoxy each with up to to 4 carbon atoms, trifluoromethyl, trifluoromethoxy, Trifluormethylthio or can be substituted by a group of the formula - _NR ²⁴ R ²⁵ , wherein R ²⁴ and R ^{25 have} the abovementioned meaning of R ¹¹ and R ¹² and are the same or different with them, or the hydrocarbon radical optionally by a group of the formula - C0 ₂ -R ²⁶ , - CONR27 R28, - NR ²⁹ R ³⁰ , - NR3'-C02R32 or -NR ^33- S0 ₂ R ^{34 is} substituted, wherein R ^{26 has} the meaning of R ¹⁵ given above and is the same or different with it and _R 27, _R 28, _R 29, _R 3 ⁰ , _R 3 ¹ , R ³² , R ³³ and R ^{34 have} the meaning given above of R ¹¹ and R ¹² and are the same or different with these, or R ^{5 represents} a 5- to 7-membered, saturated or unsaturated heterocycle with up to 4 heteroatoms from the series S, N or O, which may be up to 3 times the same or different by halogen, amino, cyano, nitro or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 4 carbon atoms or substituted by C ₁ -C ₄ mono-or - dialkylamino, or R ^{5 represents} a group of the formula DR ³⁵ , in which D represents the CO or S (O) _h group or an oxygen atom, in which h represents a number 0, 1 or 2, and _R 3 ⁵ is aryl having 6 to 10 carbon atoms or a 5-to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms from the series S, N or O, which are optionally substituted up to 3 times in an identical or different manner by halogen, Amino, cyano, nitro or substituted by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio, each having up to 4 carbon atoms, or by C ₁ -C ₄ mono- or dialkylamino, or _R 3 ^{5 is} hydrogen or a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical with up to 8 carbon atoms, which is optionally interrupted by oxygen or sulfur,
and which is optionally substituted by halogen, aryl, aryloxy or arylthio each having 6 to 10 carbon atoms or by a 5 to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms from the series S, N or O, the cycles being in turn can be substituted by halogen, trifluoromethyl, methyl, methoxy, nitro or methylthio, or
is substituted by a group of the formula - NR36R37 wherein R ³⁶ and R ^{37 have} the meaning of R ¹¹ and R ¹² given above and are the same or different with this,
and their salts,
with the proviso that R ^{5 must} not represent optionally halogen-substituted pyridyl or thienyl,
characterized in that in the event that R ^{3 represents} cyano, nitro or formyl, [A] compounds of the general formula (11)

in which R ^{5 has} the meaning given above, first with acyl compounds of the general formula (III)
R ^3- CO-CH ₂ -R ⁴ (III)
in which R ³ and R ^{4 have} the meaning given above optionally isolating the ylidene compounds of the general formula (IV)

in which R ³ , R ⁴ and R ^{5 have} the meaning given above reacted, then with compounds of the formula (V)

in which R ¹ and R ^{2 have} the meaning given above,
and a reactive ammonium compound, or directly with enamino compounds of the general formula (VI)

in which R ¹ and R ^{2 have} the meaning given above, reacted in inert solvents, and [B] Compounds of the general formula (II) first with compounds of the general formula (V), if appropriate with isolation of the ylidene compounds of the general formula (VII)

in which R ¹ , R ² and R ^{5 have} the meaning given above, reacted and then either with compounds of the general formula (III) in the presence of ammonium compounds or directly with compounds of the general formula (VIII)

in which R ³ and R ^{4 have} the meaning given above, implements or [C] in the case where R ³ and R ⁴ together are a radical of the formula

form,
wherein E 'represents an oxygen or sulfur atom, initially by the methods listed under [A] and [B], compounds of the general formula (IX)

in which R ¹ , R ² and R ^{5 have} the meaning given above, L represents C1-C4-alkyl
and T represents C ₁ -C ₄ -acyloxy or acylthio,
produces and then carries out a basic or acidic ring closure according to known methods,
or [D] that in the case that E represents the —CH ₂ group, compounds of the general formula (II), first with acyl compounds of the general formula (X)

in which R ^{2 has} the meaning given above
and L has the meaning of R ¹ given above, where in the case of the hydroxyl and / or amino functions, these are optionally in protected form, optionally with isolation of the ylidene compounds of the general formula (XI)

in which R ² , R ⁵ and L have the meaning given above reacted, then with the compound of formula (XII)

and a reactive ammonium compound, optionally with isolation of the intermediates of the general formula (XIII)

in which R ² , R ³ and L have the meaning given above, reacted in inert solvents, and then in a last step, optionally in the presence of an auxiliary, separates water. 6. Compounds of general formula (I) according to claim 1 for use in the treatment of cardiovascular diseases. 7. Medicament containing at least one compound of general formula (I) according to claim 1. 8. A process for the preparation of medicaments, characterized in that at least one compound of the general formula (I) according to claim 1 is converted, if appropriate, with customary auxiliaries and excipients into a suitable application form. 9. Use of compounds of general formula (I) according to claim 1 in medicaments with positive ionotropic activity. 10. Aldehydes of the general formula (11)

in which R ^{5 represents} a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical with up to 12 carbon atoms, which is optionally interrupted up to 2 times the same or different by oxygen or sulfur, and which is optionally up to 3 times the same or different Cycloalkyl having 3 to 8 carbon atoms, straight-chain or branched acyloxy having up to 4 carbon atoms, halogen, nitro, cyano, hydroxy or by aryl, aryloxy or arylthio each having 6 to 10 carbon atoms or by a 5 to 7-membered, saturated or unsaturated optionally condensed heterocycle is substituted with up to 5 heteroatoms from the series S, N or 0, the cycles themselves being up to 3 times the same or different by halogen, cyano, nitro, hydroxyl or by straight chain straight or branched alkyl or alkoxy each having up to 4 carbon atoms, trifluoromethyl, trifluoromethoxy, trifluoromethylthio or can be substituted by a group of the formula - _NR ²⁴ R ²⁵ , in which R ²⁴ and R ^{25 have} the meaning given above of R11 and R ¹² and are the same or different with it, wherein R ¹¹ and R ¹² together, including the nitrogen atom, form a 3- to 8-membered, saturated or unsaturated heterocycle which may be interrupted by an oxygen atom or by a radical of the formula S (O) _d , - CO - or - NR ¹⁵ can in what d represents a number 0, 1 or 2, _R ^{15 is} hydrogen or aryl having 6 to 10 carbon atoms, optionally up to 2 times the same or different by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl each having up to 8 carbon atoms, haloalkyl, haloalkoxy or haloalkylthio is each substituted with up to 4 carbon atoms, or is a cyclic, saturated or unsaturated, straight-chain or branched hydrocarbon radical having up to 8 carbon atoms, which is optionally by hydroxyl, halogen or aryl having 6 to 10 carbon atoms or a 5- to 7-membered , saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O is substituted, the cycles themselves being up to 2 times identical or different by halogen, cyano or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, Haloalkyl, haloalkoxy or haloalkylthio, each with up can be substituted to 4 carbon atoms,
and the heterocycle optionally by straight-chain or branched alkoxy or alkylthio each having up to 4 carbon atoms, halogen, aryl having 6 to 10 carbon atoms, a 5 to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms from the series S, N or O or is substituted by straight-chain or branched alkyl having up to 4 carbon atoms, which in turn can be substituted by aryl having 6 to 10 carbon atoms, or the hydrocarbon radical optionally by a group of the formula - C0 ₂ -R ²⁶ , - CONR27 R28, - NR ²⁹ R ³⁰ , - NR3'-C02R32 or -NR ^33- S0 _2R ^{34 is} substituted, wherein R ^{26 has} the meaning of R ¹⁵ given above and is the same or different with it and _R 27, _R 28, _R 29, _R 30, _R 3 ¹ , _R 3 ² , _R 33 and R ^{34 have} the meaning given above of R ¹¹ and R ¹² and are the same or different with them, or R ^{5 represents} a 5- to 7-membered, saturated or unsaturated heterocycle with up to 4 heteroatoms from the series S, N or O, which may optionally contain up to 3- is identical or differently substituted by halogen, amino, cyano, nitro or by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 4 carbon atoms or by C1-C4-mono- or dialkylamino, or R ^{5 represents} a group of the formula DR ³⁵ , in which D represents the CO or S (O) _h group or an oxygen atom, in which h represents a number 0, 1 or 2, and _R 3 ⁵ is aryl having 6 to 10 carbon atoms or a 5-to 7-membered, saturated or unsaturated heterocycle having up to 3 heteroatoms from the series S, N or O, which are optionally substituted up to 3 times in an identical or different manner by halogen, Amino, cyano, nitro or substituted by straight-chain or branched alkyl, alkoxy, alkylthio, alkoxycarbonyl, haloalkyl, haloalkoxy or haloalkylthio each having up to 4 carbon atoms or by C1-C4-mono-or-dialkylamino, or _R 3 ^{5 is} hydrogen or a cyclic, straight-chain or branched, saturated or unsaturated hydrocarbon radical having up to 8 carbon atoms, which is optionally interrupted by oxygen or sulfur, and which is optionally halogen, aryl, aryloxy or arylthio, each having 6 to 10 carbon atoms or is substituted by a 5- to 7-membered, saturated or unsaturated heterocycle with up to 3 heteroatoms from the series S, N or O, where the cycles in turn can be substituted by halogen, trifluoromethyl, methyl, methoxy, nitro or methylthio, or is substituted by a group of the formula - NR36R37 wherein R ³⁶ and R ^{37 have} the meaning of R ¹¹ and R ¹² given above and are the same or different with this,
with the proviso that R ^{5 may} not represent optionally halogen-substituted pyridyl or thienyl. 11. A process for the preparation of compounds of general formula (11) according to claim 10, characterized in that 4-amino-3-hydroxyphthalide of the formula (XIV)

either after isolation or directly in situ after hydrogenation of 4-nitro-3-hydroxyphthalide of the formula (XV)

with compounds of the general formula (XVI)

cyclized to compounds of general formula (XVII)

These are then converted into the alcohols of the general formula (XVIII) using customary reducing agents, such as, for example, lithium aluminum hydride or a mixed anhydride with sodium borohydride.

transferred and then either after isolation or directly in situ with oxidizing agents such as manganese dioxide to compounds of the general formula (II), wherein R ^{5 has} the meaning given in claim 10.